Behcet disease

Summary

Behcet disease (MONDO:0007191) is a disease with 43 cohort genes (79 GWAS associations across 17 studies) and 82 clinical trials. The dominant Reactome pathway is Interleukin-35 Signalling (3 cohort genes). Top therapeutic interventions include apremilast, canakinumab, and daclizumab.

At a glance

• Prevalence: 1-9 / 100 000 (United States) [Orphanet-validated]
• Cohort genes: 43
• GWAS associations: 79
• ClinVar variants: 22
• Phenotypes (HPO): 85
• Clinical trials: 82

Clinical features

Epidemiology

Prevalence records

18 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 1 000 000	0.66	Spain	Validated
Annual incidence	1-9 / 1 000 000	0.24	Italy	Validated
Annual incidence	1-9 / 1 000 000	0.58	Iran, Islamic Republic of	Validated
Annual incidence	1-9 / 1 000 000	0.8	Taiwan, Province of China	Validated
Annual incidence	1-9 / 100 000	1.51	Korea, Republic of	Validated
Point prevalence	1-9 / 100 000	5.2	United States	Validated
Point prevalence	1-9 / 100 000	7.1	France	Validated
Point prevalence	1-9 / 100 000	3.8	Italy	Validated
Point prevalence	1-5 / 10 000	11.1	United Kingdom	Validated
Point prevalence	1-9 / 100 000	1.2	Sweden	Validated
Point prevalence	1-9 / 100 000	1.5	Portugal	Validated
Point prevalence	1-5 / 10 000	10	Japan	Validated
Point prevalence	>1 / 1000	225	Turkey	Validated
Point prevalence	1-5 / 10 000	16.7	Iran, Islamic Republic of	Validated
Point prevalence	1-5 / 10 000	15.2	Israel	Validated
Point prevalence	1-5 / 10 000	20	Saudi Arabia	Validated
Point prevalence	1-9 / 100 000		Europe	Not yet validated
Point prevalence	1-9 / 100 000	1.4	Taiwan, Province of China	Not yet validated

Signs & symptoms

Clinical features (HPO)

85 HPO clinical features (Orphanet curated; top 50 by frequency):

HPO ID	Term	Frequency
HP:0000155	Oral ulcer	Very frequent (80-99%)
HP:0000613	Photophobia	Very frequent (80-99%)
HP:0001287	Meningitis	Very frequent (80-99%)
HP:0001369	Arthritis	Very frequent (80-99%)
HP:0001482	Subcutaneous nodule	Very frequent (80-99%)
HP:0001945	Fever	Very frequent (80-99%)
HP:0002017	Nausea and vomiting	Very frequent (80-99%)
HP:0002076	Migraine	Very frequent (80-99%)
HP:0002633	Vasculitis	Very frequent (80-99%)
HP:0003326	Myalgia	Very frequent (80-99%)
HP:0011107	Recurrent aphthous stomatitis	Very frequent (80-99%)
HP:0012378	Fatigue	Very frequent (80-99%)
HP:0100796	Orchitis	Very frequent (80-99%)
HP:0200034	Papule	Very frequent (80-99%)
HP:0001061	Acne	Frequent (30-79%)
HP:0001269	Hemiparesis	Frequent (30-79%)
HP:0001288	Gait disturbance	Frequent (30-79%)
HP:0001289	Confusion	Frequent (30-79%)
HP:0002027	Abdominal pain	Frequent (30-79%)
HP:0002239	Gastrointestinal hemorrhage	Frequent (30-79%)
HP:0002315	Headache	Frequent (30-79%)
HP:0002638	Superficial thrombophlebitis	Frequent (30-79%)
HP:0002829	Arthralgia	Frequent (30-79%)
HP:0003249	Genital ulcers	Frequent (30-79%)
HP:0003565	Elevated erythrocyte sedimentation rate	Frequent (30-79%)
HP:0004936	Venous thrombosis	Frequent (30-79%)
HP:0007813	Nongranulomatous uveitis	Frequent (30-79%)
HP:0008066	Abnormal blistering of the skin	Frequent (30-79%)
HP:0011227	Elevated circulating C-reactive protein concentration	Frequent (30-79%)
HP:0012121	Panuveitis	Frequent (30-79%)
HP:0012219	Erythema nodosum	Frequent (30-79%)
HP:0012649	Increased inflammatory response	Frequent (30-79%)
HP:0025532	Positive pathergy test	Frequent (30-79%)
HP:0100326	Immunologic hypersensitivity	Frequent (30-79%)
HP:0200039	Pustule	Frequent (30-79%)
HP:0002024	Malabsorption	Occasional (5-29%)
HP:0002039	Anorexia	Occasional (5-29%)
HP:0002102	Pleuritis	Occasional (5-29%)
HP:0002105	Hemoptysis	Occasional (5-29%)
HP:0002113	Pulmonary infiltrates	Occasional (5-29%)
HP:0002202	Pleural effusion	Occasional (5-29%)
HP:0002204	Pulmonary embolism	Occasional (5-29%)
HP:0002321	Vertigo	Occasional (5-29%)
HP:0002354	Memory impairment	Occasional (5-29%)
HP:0002376	Developmental regression	Occasional (5-29%)
HP:0002383	Infectious encephalitis	Occasional (5-29%)
HP:0002516	Increased intracranial pressure	Occasional (5-29%)
HP:0002637	Cerebral ischemia	Occasional (5-29%)
HP:0002716	Lymphadenopathy	Occasional (5-29%)
HP:0003401	Paresthesia	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Behcet disease
Mondo ID	MONDO:0007191
EFO	EFO:0003780
MeSH	D001528
OMIM	109650
Orphanet	117
DOID	DOID:13241
ICD-11	1668927157
NCIT	C34416
SNOMED CT	310701003
UMLS	C0004943
MedGen	2568
GARD	0000848
MedDRA	10004213
Anatomy (UBERON)	UBERON:0001981
Is cancer (heuristic)	no

Also known as: BD · Bechet syndrome · Behcet disease · Behcet syndrome · Behcet’s syndrome · Behçet disease · Behçet syndrome · Behçet’s disease · Behçet’s syndrome · Behçet-Adamantiades syndrome · Behçet’s disease · Morbus Behçet’s syndrome · silk road disease

Data availability: 22 ClinVar variants · 79 GWAS associations (17 studies) · 21 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Behcet disease

Related subtypes (1183): Neu-Laxova syndrome, inclusion body myopathy with Paget disease of bone and frontotemporal dementia, syndromic intellectual disability, abdominal obesity-metabolic syndrome, fibrogenesis imperfecta ossium, Fanconi renotubular syndrome, palindromic rheumatism, hepatorenal syndrome, Potter sequence, vertebral artery insufficiency, sick sinus syndrome, Tietze syndrome, toxic shock syndrome, capillary leak syndrome, dumping syndrome, FG syndrome, basilar artery insufficiency, long QT syndrome, Treacher-Collins syndrome, superior mesenteric artery syndrome, disappearing bone disease, Brown-Sequard syndrome, Froelich syndrome, diffuse infiltrative lymphocytosis syndrome, Capgras syndrome, compartment syndrome, central sleep apnea syndrome, irritable bowel syndrome, nephrotic syndrome, myalgic encephalomeyelitis/chronic fatigue syndrome, acute coronary syndrome, fibromyalgia, substance withdrawal syndrome, acute chest syndrome, Barre-Lieou syndrome, cauda equina syndrome, Kluver-Bucy syndrome, Miller Fisher syndrome, persian gulf syndrome, Reye syndrome, thoracic outlet syndrome, Waterhouse-Friderichsen syndrome, Wissler syndrome, acute respiratory distress syndrome, Achenbach syndrome, miliaria, anterior spinal artery syndrome, burning mouth syndrome, dry eye syndrome, empty sella syndrome, euthyroid sick syndrome, lateral medullary syndrome, subclavian steal syndrome, tarsal tunnel syndrome, tethered spinal cord syndrome, branchio-oto-renal syndrome, prune belly syndrome, Achard syndrome, alopecia-epilepsy-pyorrhea-intellectual disability syndrome, Finnish type amyloidosis, Angelman syndrome, aniridia-absent patella syndrome, ankyloblepharon filiforme adnatum-cleft palate syndrome, Townes-Brocks syndrome, obstructive sleep apnea syndrome, Lown-Ganong-Levine syndrome, brachydactyly-arterial hypertension syndrome, brachydactyly type A2, fibular aplasia-ectrodactyly syndrome, brachydactyly-nystagmus-cerebellar ataxia syndrome, Sillence syndrome, Brachymorphism-onychodysplasia-dysphalangism syndrome, brachytelephalangy-dysmorphism-Kallmann syndrome, dilated cardiomyopathy 1A, cat-eye syndrome, cerebrocostomandibular syndrome, Alagille syndrome, autosomal dominant chondrodysplasia punctata, cleidocranial dysplasia 1, cleidorhizomelic syndrome, cochleosaccular degeneration-cataract syndrome, renal coloboma syndrome, Cri-du-chat syndrome, autosomal dominant deafness - onychodystrophy syndrome, cerebral arteriopathy with subcortical infarcts and leukoencephalopathy, Duane retraction syndrome, 3-M syndrome, dyschondrosteosis-nephritis syndrome, hereditary benign intraepithelial dyskeratosis, encephalopathy, recurrent, of childhood, Camurati-Engelmann disease, Felty syndrome, chromosome 16p12.1 deletion syndrome, 520kb, Frasier syndrome, Gamstorp-Wohlfart syndrome, Tourette syndrome, glaucoma-sleep apnea syndrome, renal cysts and diabetes syndrome, hypotrichosis-lymphedema-telangiectasia syndrome (grouping), GMS syndrome, gray platelet syndrome, hand-foot-genital syndrome, facial hemiatrophy, Bencze syndrome, alpha thalassemia-intellectual disability syndrome type 1, Gilbert syndrome, mullerian duct anomalies-limb anomalies syndrome, hypoparathyroidism-deafness-renal disease syndrome, chromosome 18p deletion syndrome, Pallister-Hall syndrome, ichthyosis-cheek-eyebrow syndrome, Jacobsen syndrome, palmoplantar keratoderma-hereditary motor and sensory neuropathy syndrome, palmoplantar keratoderma-esophageal carcinoma syndrome, Kleine-Levin syndrome, angioosteohypertrophic syndrome, congenital laryngeal web, Lenz-Majewski hyperostotic dwarfism, Noonan syndrome with multiple lentigines, lymphedema-cerebral arteriovenous anomaly syndrome, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, yellow nail syndrome, lymphedema-distichiasis syndrome, Nager acrofacial dysostosis, jaw-winking syndrome, Marfan syndrome, Melkersson-Rosenthal syndrome, metaphyseal chondrodysplasia, Jansen type, Schmid metaphyseal chondrodysplasia, metaphyseal dysplasia-maxillary hypoplasia-brachydacty syndrome, microgastria-limb reduction defect syndrome, Mobius syndrome, muscular atrophy-ataxia-retinitis pigmentosa-diabetes mellitus syndrome, nail-patella syndrome, Schilbach-Rott syndrome, syndromic orbital border hypoplasia, Buschke-Ollendorff syndrome, nasopalpebral lipoma-coloboma syndrome, Perry syndrome, Poland syndrome, polydactyly-myopia syndrome, Greig cephalopolysyndactyly syndrome, Prader-Willi syndrome, Guttmacher syndrome, Currarino triad, Hutchinson-Gilford progeria syndrome, progeria-short stature-pigmented nevi syndrome, Liddle syndrome, exfoliation syndrome, ptosis-strabismus-ectopic pupils syndrome, radial hypoplasia-triphalangeal thumbs-hypospadias-maxillary diastema syndrome, radial ray hypoplasia-choanal atresia syndrome, Roussy-Levy syndrome, Silver-Russell syndrome, Ruvalcaba syndrome, oculodental syndrome, Rutherfurd type, aplasia of lacrimal and salivary glands, scalp defects-postaxial polydactyly syndrome, ulnar-mammary syndrome, septooptic dysplasia, Czeizel-Losonci syndrome, polycystic ovary syndrome, stiff-person syndrome, syndactyly-polydactyly-ear lobe syndrome, HELLP syndrome, double uterus-hemivagina-renal agenesis syndrome, VACTERL/vater association, posterior fusion of lumbosacral vertebrae-blepharoptosis syndrome, ptosis-vocal cord paralysis syndrome, Freeman-Sheldon syndrome, Williams syndrome, Denys-Drash syndrome, Wolf-Hirschhorn syndrome, ablepharon macrostomia syndrome, acrocallosal syndrome, PAGOD syndrome, alopecia - intellectual disability syndrome, mitochondrial DNA depletion syndrome 4a, Alstrom syndrome, aniridia-cerebellar ataxia-intellectual disability syndrome, aniridia-renal agenesis-psychomotor retardation syndrome, aplasia cutis congenita-intestinal lymphangiectasia syndrome, fetal akinesia deformation sequence, blepharophimosis-ptosis-esotropia-syndactyly-short stature syndrome, Bloom syndrome, Elsahy-Waters syndrome, campomelia, Cumming type, camptomelic syndrome, long-limb type, congenital cataract-ichthyosis syndrome, colobomatous optic disc-macular atrophy-chorioretinopathy syndrome, hepatic fibrosis-renal cysts-intellectual disability syndrome, Charcot-Marie-Tooth disease-hearing loss-intellectual disability syndrome, CHARGE syndrome, Aagenaes syndrome, infantile choroidocerebral calcification syndrome, Yunis-Varon syndrome, corneal dystrophy-perceptive deafness syndrome, cortical blindness-intellectual disability-polydactyly syndrome, Crigler-Najjar syndrome, cataract-nephropathy-encephalopathy syndrome, Fraser syndrome, cystic fibrosis-gastritis-megaloblastic anemia syndrome, cystinuria, DOORS syndrome, high myopia-sensorineural deafness syndrome, dermochondrocorneal dystrophy, nephrogenic diabetes insipidus-intracranial calcification syndrome, diverticulosis of bowel, hernia, and retinal detachment, Dyggve-Melchior-Clausen disease, cerebellar ataxia, intellectual disability, and dysequilibrium, ectrodactyly-polydactyly syndrome, Bonnemann-Meinecke-Reich syndrome, epidermolysis bullosa simplex 5B, with muscular dystrophy, Wolcott-Rallison syndrome, ermine phenotype, eyebrow duplication-syndactyly syndrome, Fanconi-like syndrome, gingival fibromatosis-facial dysmorphism syndrome, frontofacionasal dysplasia, Fryns syndrome, German syndrome, Bernard-Soulier syndrome, triple-A syndrome, Grubben-de Cock-Borghgraef syndrome, mullerian derivatives-lymphangiectasia-polydactyly syndrome, Hirschsprung disease-hearing loss-polydactyly syndrome, Hirschsprung disease-nail hypoplasia-dysmorphism syndrome, Holzgreve-Wagner-Rehder syndrome, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, growth delay-hydrocephaly-lung hypoplasia syndrome, Dubin-Johnson syndrome, ornithine translocase deficiency, acrofrontofacionasal dysostosis 2, hypertrichotic osteochondrodysplasia Cantu type, hypergonadotropic hypogonadism-cataract syndrome, primary hypergonadotropic hypogonadism-partial alopecia syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, hypospadias-intellectual disability, Goldblatt type syndrome, Bamforth-Lazarus syndrome, ichthyosis-hepatosplenomegaly-cerebellar degeneration syndrome, ichthyosis-intellectual disability-dwarfism-renal impairment syndrome, Vici syndrome, channelopathy-associated congenital insensitivity to pain, autosomal recessive, Joubert syndrome with oculorenal defect, oculocerebrofacial syndrome, Kaufman type, Landau-Kleffner syndrome, laryngo-onycho-cutaneous syndrome, Laurence-Moon syndrome, Donohue syndrome, Miller-Dieker lissencephaly syndrome, Marinesco-Sjogren syndrome, Frank-Ter Haar syndrome, Mietens syndrome, mesomelic dwarfism-cleft palate-camptodactyly syndrome, metaphyseal chondrodysplasia-retinitis pigmentosa syndrome, metaphyseal dysostosis-intellectual disability-conductive deafness syndrome, microcephalic primordial dwarfism, Toriello type, Say-Barber-Miller syndrome, microcephaly and chorioretinopathy 1, Galloway-Mowat syndrome, microtia with meatal atresia and conductive deafness, mucopolysaccharidosis type 6, mulibrey nanism, lethal multiple pterygium syndrome, lethal congenital contracture syndrome 1, Schwartz-Jampel syndrome, Nathalie syndrome, nephronophthisis 1, nephropathy - deafness - hyperparathyroidism syndrome, nephrosis-deafness-urinary tract-digital malformations syndrome, Netherton syndrome, Norman-Roberts syndrome, cloacal exstrophy, ichthyosis-oral and digital anomalies syndrome, Primrose syndrome, familial osteodysplasia, Anderson type, multicentric osteolysis, nodulosis, and arthropathy, osteopenia-intellectual disability-sparse hair syndrome, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, Parana hard-skin syndrome, PEHO syndrome, Imerslund-Grasbeck syndrome, Peters plus syndrome, pili torti-developmental delay-neurological abnormalities syndrome, Rabson-Mendenhall syndrome, postaxial acrofacial dysostosis, Gitelman syndrome, Wiedemann-Rautenstrauch syndrome, Acrootoocular syndrome, holoprosencephaly-postaxial polydactyly syndrome, autosomal recessive multiple pterygium syndrome, Perlman syndrome, retinitis pigmentosa-intellectual disability-deafness-hypogenitalism syndrome, EEC syndrome, SHORT syndrome, Sjogren syndrome, spastic tetraplegia-retinitis pigmentosa-intellectual disability syndrome, corneal-cerebellar syndrome, spastic ataxia-corneal dystrophy syndrome, spondylocostal dysostosis-anal and genitourinary malformations syndrome, familial infantile bilateral striatal necrosis, subaortic stenosis-short stature syndrome, thrombocytopenia-absent radius syndrome, thyrocerebrorenal syndrome, Pendred syndrome, VACTERL with hydrocephalus, Weaver syndrome, Werner syndrome, Wernicke-Korsakoff syndrome, wooly hair-hypotrichosis-everted lower lip-outstanding ears syndrome, de Sanctis-Cacchione syndrome, corpus callosum agenesis-abnormal genitalia syndrome, Alport syndrome-intellectual disability-midface hypoplasia-elliptocytosis syndrome, X-linked lissencephaly with abnormal genitalia, X-linked myotubular myopathy-abnormal genitalia syndrome, Christianson syndrome, Armfield syndrome, Lesch-Nyhan syndrome, Atkin-Flaitz syndrome, alpha-thalassemia-myelodysplastic syndrome, deafness-intellectual disability, Martin-Probst type syndrome, fragile X-associated tremor/ataxia syndrome, fragile X syndrome, syndactyly-telecanthus-anogenital and renal malformations syndrome, X-linked dominant chondrodysplasia, Chassaing-Lacombe type, X-linked central congenital hypothyroidism with late-onset testicular enlargement, Meester-Loeys syndrome, Arts syndrome, X-linked mandibulofacial dysostosis, Abruzzo-Erickson syndrome, Aicardi syndrome, craniofrontonasal syndrome, deafness-hypogonadism syndrome, X-linked corneal dermoid, immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome, hydrocephaly-cerebellar agenesis syndrome, keratosis follicularis-dwarfism-cerebral atrophy syndrome, laryngeal abductor paralysis-intellectual disability syndrome, oculocerebrorenal syndrome, Menkes disease, paraplegia-intellectual disability-hyperkeratosis syndrome, mucopolysaccharidosis type 2, orofaciodigital syndrome I, otopalatodigital syndrome type 1, Pallister-W syndrome, Rett syndrome, SCARF syndrome, Simpson-Golabi-Behmel syndrome, torticollis-keloids-cryptorchidism-renal dysplasia syndrome, trigonocephaly-short stature-developmental delay syndrome, ulnar hypoplasia-split foot syndrome, van den Bosch syndrome, Wildervanck syndrome, Kearns-Sayre syndrome, MELAS syndrome, MERRF syndrome, Pearson syndrome, proximal tubulopathy-diabetes mellitus-cerebellar ataxia syndrome, pancreatic hypoplasia-diabetes-congenital heart disease syndrome, chondrodysplasia-pseudohermaphroditism syndrome, Qazi Markouizos syndrome, familial developmental dysphasia, atrioventricular defect-blepharophimosis-radial and anal defect syndrome, CODAS syndrome, lethal hemolytic anemia-genital anomalies syndrome, HEC syndrome, anophthalmia plus syndrome, infundibulopelvic stenosis-multicystic kidney syndrome, Ayme-Gripp syndrome, dilated cardiomyopathy 1E, diaphragmatic defect-limb deficiency-skull defect syndrome, skeletal dysplasia-epilepsy-short stature syndrome, Potocki-Shaffer syndrome, amelia cleft lip palate hydrocephalus iris coloboma, human HOXA1 syndromes, dyssegmental dysplasia-glaucoma syndrome, lung agenesis-heart defect-thumb anomalies syndrome, tetrasomy 12p, chromosome 18q deletion syndrome, lymphedema-atrial septal defects-facial changes syndrome, infantile convulsions and choreoathetosis, RHYNS syndrome, Pierre Robin sequence with pectus excavatum and rib and scapular anomalies, colobomatous macrophthalmia-microcornea syndrome, Marshall-Smith syndrome, distal monosomy 13q, MPI-congenital disorder of glycosylation, camptodactyly, myopia, and fibrosis of the medial rectus muscle of eye, radioulnar synostosis-microcephaly-scoliosis syndrome, blepharophimosis - intellectual disability syndrome, SBBYS type, complex regional pain syndrome type 1, temtamy preaxial brachydactyly syndrome, Diamond-Blackfan anemia 2, genitopatellar syndrome, Phelan-McDermid syndrome, hypotonia-cystinuria syndrome, DNA ligase IV deficiency, Hurler syndrome, Hurler-Scheie syndrome, Scheie syndrome, Duane-radial ray syndrome, psoriatic arthritis, neonatal ichthyosis-sclerosing cholangitis syndrome, skin fragility-woolly hair-palmoplantar keratoderma syndrome, tubulointerstitial nephritis and uveitis syndrome, caudal duplication, sweet syndrome, ichthyosis prematurity syndrome, Meacham syndrome, BNAR syndrome, PCWH syndrome, foveal hypoplasia - optic nerve decussation defect - anterior segment dysgenesis syndrome, B-cell immunodeficiency, distal limb anomalies, and urogenital malformations, MEDNIK syndrome, Cerebrorenodigital syndrome, fetal valproate syndrome, Goldberg-Shprintzen syndrome, Al-Gazali syndrome, CEDNIK syndrome, osteosclerosis-ichthyosis-premature ovarian failure syndrome, cortical dysplasia-focal epilepsy syndrome, DK1-congenital disorder of glycosylation, Potocki-Lupski syndrome, Pitt-Hopkins syndrome, XFE progeroid syndrome, deafness-infertility syndrome, COG1-congenital disorder of glycosylation, autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome, microtia-eye coloboma-imperforation of the nasolacrimal duct syndrome, mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria, ANE syndrome, CLOVES syndrome, Hirschsprung disease-ganglioneuroblastoma syndrome, parkinsonism-dystonia, infantile, alpha 1-antitrypsin deficiency, COG5-congenital disorder of glycosylation, chromosome 13q14 deletion syndrome, deafness-lymphedema-leukemia syndrome, microcephaly-capillary malformation syndrome, EDICT syndrome, peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome, hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism, IMAGe syndrome, short stature-onychodysplasia-facial dysmorphism-hypotrichosis syndrome, microcephalic primordial dwarfism, Alazami type, intellectual disability-strabismus syndrome, estrogen resistance syndrome, Hartsfield-Bixler-Demyer syndrome, severe dermatitis-multiple allergies-metabolic wasting syndrome, alacrima, achalasia, and intellectual disability syndrome, familial episodic pain syndrome with predominantly lower limb involvement, congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome, diffuse cerebral and cerebellar atrophy - intractable seizures - progressive microcephaly syndrome, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, tall stature-scoliosis-macrodactyly of the great toes syndrome, intellectual disability, autosomal dominant 29, intellectual disability, autosomal dominant 30, congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome, retinitis pigmentosa-juvenile cataract-short stature-intellectual disability syndrome, polyendocrine-polyneuropathy syndrome, chronic atrial and intestinal dysrhythmia, motor developmental delay due to 14q32.2 paternally expressed gene defect, peeling skin-leukonuchia-acral punctate keratoses-cheilitis-knuckle pads syndrome, mandibulofacial dysostosis with alopecia, epilepsy with myoclonic atonic seizures, short stature, microcephaly, and endocrine dysfunction, progressive microcephaly-seizures-cortical blindness-developmental delay syndrome, PMP22-RAI1 contiguous gene duplication syndrome, acute infantile liver failure-cerebellar ataxia-peripheral sensory motor neuropathy syndrome, familial progressive retinal dystrophy-iris coloboma-congenital cataract syndrome, macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome, Luscan-Lumish syndrome, even-plus syndrome, MIRAGE syndrome, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, intellectual disability-epilepsy-extrapyramidal syndrome, 48,XXYY syndrome, FRAXF syndrome, complex hereditary spastic paraplegia, aniridia-ptosis-intellectual disability-familial obesity syndrome, aniridia - intellectual disability syndrome, ankyloblepharon filiforme-imperforate anus syndrome, pentasomy X, Bardet-Biedl syndrome, anophthalmia-megalocornea-cardiopathy-skeletal anomalies syndrome, Bartter syndrome, arachnodactyly-intellectual disability-dysmorphism syndrome, ataxia-photosensitivity-short stature syndrome, Brugada syndrome, Feingold syndrome, cardiomyopathy-cataract-hip spine disease syndrome, cataract - microcornea syndrome, autism-facial port-wine stain syndrome, cataract-intellectual disability-anal atresia-urinary defects syndrome, cataract-deafness-hypogonadism syndrome, syndromic craniosynostosis, drug rash with eosinophilia and systemic symptoms, multicentric reticulohistiocytosis, hereditary sensory and autonomic neuropathy with deafness and global delay, craniofacial microsomia, ring chromosome 10, Coffin-Siris syndrome, corpus callosum agenesis-double urinary collecting system syndrome, short rib-polydactyly syndrome, oromandibular-limb anomalies syndrome, hemophagocytic syndrome, cataract-glaucoma syndrome, diencephalic syndrome, hypereosinophilic syndrome, distal trisomy 14q, intellectual disability-cataracts-kyphosis syndrome, progressive familial intrahepatic cholestasis, thoraco-abdominal enteric duplication, oculomaxillofacial dysostosis, growth hormone insensitivity syndrome, syndromic dyslipidemia, macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss, epiphyseal dysplasia-hearing loss-dysmorphism syndrome, eosinophilic granulomatosis with polyangiitis, axial mesodermal dysplasia spectrum, fetal hydantoin syndrome, vitamin K-antagonist embryofetopathy, fetal alcohol syndrome, methimazole embryofetopathy, Evans syndrome, Cornelia de Lange syndrome, cleft lip-retinopathy syndrome, cleft lip/palate-deafness-sacral lipoma syndrome, Crandall syndrome, syndromic microphthalmia, Cole-Carpenter syndrome, myotonic syndrome, Guillain-Barre syndrome, atypical hemolytic-uremic syndrome, Hennekam syndrome, Hernández-Aguirre Negrete syndrome, nodular neuronal heterotopia, Hirschsprung disease-type D brachydactyly syndrome, holoprosencephaly, hydrocephalus-obesity-hypogonadism syndrome, hydrocephalus-blue sclerae-nephropathy syndrome, xeroderma pigmentosum-Cockayne syndrome complex, Joubert syndrome with ocular defect, hypogonadism-mitral valve prolapse-intellectual disability syndrome, hypogonadotropic hypogonadism-retinitis pigmentosa syndrome, hypotrichosis-intellectual disability, Lopes type, congenital ichthyosis-microcephalus-tetraplegia syndrome, Hughes-Stovin syndrome, heart-hand syndrome, ptosis-upper ocular movement limitation-absence of lacrimal punctum syndrome, syndromic agammaglobulinemia, isotretinoin syndrome, microcornea-posterior megalolenticonus-persistent fetal vasculature-coloboma syndrome, Kabuki syndrome, Kenny-Caffey syndrome, muscular pseudohypertrophy-hypothyroidism syndrome, Kousseff syndrome, limb body wall complex, Lennox-Gastaut syndrome, Lowe-Kohn-Cohen syndrome, macrocephaly-short stature-paraplegia syndrome, primary ciliary dyskinesia, familial intestinal malrotation-facial anomalies syndrome, primary hypertrophic osteoarthropathy, Melhem-Fahl syndrome, lower limb deficiency-hypospadias syndrome, 8p23.1 microdeletion syndrome, sickle cell-beta-thalassemia disease syndrome, sickle cell-hemoglobin c disease syndrome, sickle cell-hemoglobin d disease syndrome, sickle cell-hemoglobin E disease syndrome, hereditary persistence of fetal hemoglobin-sickle cell disease syndrome, microcephaly-brain defect-spasticity-hypernatremia syndrome, microcephaly-microcornea syndrome, Seemanova type, Meier-Gorlin syndrome, Mikati-Najjar-Sahli syndrome, shoulder and girdle defects-familial intellectual disability syndrome, myopathy-growth delay-intellectual disability-hypospadias syndrome, Fuchs heterochromic iridocyclitis, microcephalic osteodysplastic primordial dwarfism types I and III, osteochondrodysplatic nanism-deafness-retinitis pigmentosa syndrome, arthrogryposis-renal dysfunction-cholestasis syndrome, oculo-skeletal-renal syndrome, olivopontocerebellar atrophy-deafness syndrome, Opitz G/BBB syndrome, imperforate oropharynx-costo vetebral anomalies syndrome, Bruck syndrome, osteoporosis-macrocephaly-blindness-joint hyperlaxity syndrome, calciphylaxis, recessive intellectual disability-motor dysfunction-multiple joint contractures syndrome, X-linked ichthyosis syndrome, autoimmune polyendocrinopathy, renal caliceal diverticuli-deafness syndrome, tempi syndrome, syndromic oculocutaneous albinism, short stature-deafness-neutrophil dysfunction-dysmorphism syndrome, congenital varicella syndrome, polyneuropathy-intellectual disability-acromicria-premature menopause syndrome, celiac trunk compression syndrome, hypoplastic pancreas-intestinal atresia-hypoplastic gallbalder syndrome, fetal cytomegalovirus syndrome, Reunion island Larsen syndrome, 46,XX disorder of sex development-anorectal anomalies syndrome, mitochondrial neurogastrointestinal encephalomyopathy, Baraitser-Winter cerebrofrontofacial syndrome, mirror polydactyly-vertebral segmentation-limbs defects syndrome, intellectual disability-hypotonia-skin hyperpigmentation syndrome, congenital hereditary facial paralysis-variable hearing loss syndrome, intellectual disability-microcephaly-phalangeal-facial abnormalities syndrome, Mayer-Rokitansky-Kuster-Hauser syndrome, developmental and speech delay due to SOX5 deficiency, Spigelian hernia-cryptorchidism syndrome, autosomal recessive leukoencephalopathy-ischemic stroke-retinitis pigmentosa syndrome, severe neonatal hypotonia-seizures-encephalopathy syndrome due to 5q31.3 microdeletion, multiple sclerosis-ichthyosis-factor VIII deficiency syndrome, X-linked spasticity-intellectual disability-epilepsy syndrome, spina bifida-hypospadias syndrome, hantavirus pulmonary syndrome, white matter hypoplasia-corpus callosum agenesis-intellectual disability syndrome, deafness-genital anomalies-metacarpal and metatarsal synostosis syndrome, hearing loss-familial salivary gland insensitivity to aldosterone syndrome, multiple synostoses syndrome, central nervous system calcification-deafness-tubular acidosis-anemia syndrome, multiple paragangliomas associated with polycythemia, syngnathia multiple anomalies, Takayasu arteritis, severe early-onset obesity-insulin resistance syndrome due to SH2B1 deficiency, spondylocostal dysostosis-hypospadias-intellectual disability syndrome, hypotrichosis-deafness syndrome, thalidomide embryopathy, trisomy X, trisomy 13, trisomy 18, umbilical cord ulceration-intestinal atresia syndrome, microcephaly-brachydactyly-kyphoscoliosis syndrome, Waardenburg syndrome, Weill-Marchesani syndrome, infantile spasms, Wolfram syndrome, epidermal nevus syndrome, digital anomalies-intellectual disability-short stature syndrome, intellectual disability-obesity-brain malformations-facial dysmorphism syndrome, Erdheim-Chester disease, Stevens-Johnson syndrome, CADDS, finger hyperphalangy - toe anomalies - severe pectus excavatum syndrome, ataxia - telangiectasia variant, growth retardation-mild developmental delay-chronic hepatitis syndrome, primary microcephaly-mild intellectual disability-young-onset diabetes syndrome, ferro-cerebro-cutaneous syndrome, dystonia-aphonia syndrome, microcephaly-complex motor and sensory axonal neuropathy syndrome, X-linked microcephaly-growth retardation-prognathism-cryptorchidism syndrome, severe intellectual disability-hypotonia-strabismus-coarse face-planovalgus syndrome, intrauterine growth restriction-short stature-early adult-onset diabetes syndrome, pseudoxanthoma elasticum-like skin manifestations with retinitis pigmentosa, familial chylomicronemia syndrome, caudal regression-sirenomelia spectrum, visceral heterotaxy, Holmes-Adie syndrome, microcephalic primordial dwarfism due to RTTN deficiency, Joubert syndrome, congenital generalized hypercontractile muscle stiffness syndrome, Kallmann syndrome, Caroli syndrome, X-linked female restricted facial dysmorphism-short stature-choanal atresia-intellectual disability, microlissencephaly-micromelia syndrome, branchiootic syndrome, Plummer-Vinson syndrome, Cushing syndrome, McCune-Albright syndrome, Meckel syndrome, SUNCT syndrome, mucopolysaccharidosis type 3, mucopolysaccharidosis type 4, congenital myasthenic syndrome, Loeys-Dietz syndrome, Alport syndrome, schisis association, Tolosa-Hunt syndrome, iridocorneal endothelial syndrome, Noonan syndrome, short fifth metacarpals-insulin resistance syndrome, progressive supranuclear palsy, benign exophthalmos syndrome, Sandifer syndrome, global developmental delay-osteopenia-ectodermal defect syndrome, tubular renal disease-cardiomyopathy syndrome, angioosteohypotrophic syndrome, 6q terminal deletion syndrome, Axenfeld-Rieger syndrome, peroxisome biogenesis disorder, ectodermal dysplasia syndrome, Seckel syndrome, Sotos syndrome, Stickler syndrome, pelvis syndrome, Susac syndrome, ischio-vertebral syndrome, BRESEK syndrome, Turner syndrome, Usher syndrome, obesity-colitis-hypothyroidism-cardiac hypertrophy-developmental delay syndrome, CREST syndrome, Sheehan syndrome, polymyalgia rheumatica, autoinflammatory syndrome, neuroleptic malignant syndrome, pituitary stalk interruption syndrome, monosomy 13q34, ring chromosome 13, 48,XXXY syndrome, 49,XXXXY syndrome, hereditary continuous muscle fiber activity, Eisenmenger syndrome, Robinow syndrome, Ehlers-Danlos syndrome, hypoplastic right heart syndrome, shone complex, 48,XYYY syndrome, subcortical band heterotopia, complex regional pain syndrome type 2, faciodigitogenital syndrome, neoplastic syndrome, paraneoplastic syndrome, post-infectious syndrome, Achard-Thiers syndrome, acral dysostosis dyserythropoiesis syndrome, agnathia-microstomia-synotia, Aksu von Stockhausen syndrome, Aloi Tomasini Isaia syndrome, temporomandibular joint dysfunction syndrome, Apert-like polydactyly syndrome, arakawa syndrome 2, arena syndrome, Arnold stickler bourne syndrome, baetz-greenwalt syndrome, bagatelle Cassidy syndrome, baker Vinters syndrome, bobble-head doll syndrome, Boerhaave syndrome, Cantu Sanchez-Corona Fragoso syndrome, Cantu Sanchez-Corona Hernandez syndrome, carbon baby syndrome, Carnevale hernandez castillo syndrome, Cartwright Nelson Fryns syndrome, Charles bonnet syndrome, Parinaud syndrome, corticobasal degeneration disorder, hair defect with photosensitivity and intellectual disability syndrome, AIDS dysmorphic syndrome, congenital acardia, acute lymphoblastic leukemia congenital sporadic aniridia, aglossia and situs inversus, agyria pachygyria polymicrogyria, agyria-pachygyria type 1, Ahumada Del Castillo syndrome, alopecia congenita keratosis palmoplantaris, alpha-mannosidosis type 1, aluminosis, Mauriac syndrome, ankle defects short stature, ankyloblepharon filiforme imperforate anus, annular constricting bands, anophthalmia cleft palate micrognathia, anophthalmia esophageal atresia cryptorchidism, anotia facial palsy cardiac defect, aortic dissection lentiginosis, childhood aortic valve stenosis, arthrogryposis IUGR thoracic dystrophy, arthrogryposis multiplex congenita CNS calcification, arthrogryposis spinal muscular atrophy, asternia, atlanto-axial fusion, atrophoderma of Pierini and Pasini, Barnicoat Baraitser syndrome, Basedow’s coma, BD syndrome, Beardwell syndrome, bhaskar jagannathan syndrome, bidirectional tachycardia, bilirubin induced brain injury in the newborn, blepharo naso facial syndrome van Maldergem type, bone dysplasia corpus callosum agenesis, brachydactyly absence of distal phalanges, brachydactyly anonychia, brachydactyly small stature face anomalies, brachydactyly tibial hypoplasia, brittle bone syndrome lethal type, bronchiectasis oligospermia, Brunsting-Perry syndrome, bruyn scheltens syndrome, burn goodship syndrome, camptodactyly joint contractures and facial skeletal dysplasia, camptodactyly vertebral fusion, Cantu Sanchez-Corona Garcia-Cruz syndrome, cardiac hydatid cysts with intracavitary expansion, cardioencephalomyopathy, cardiofacial syndrome short limbs, cardiomelic syndrome stratton Koehler type, cardiomyopathy and deafness due to tRNA lysine gene mutation, cardiomyopathy diabetes deafness, cardiomyopathy hypogonadism collagenoma syndrome, cardiomyopathy hypogonadism metabolic anomalies, cardiomyopathy spherocytosis, carpo tarsal osteolysis recessive, autosomal dominant cataract, cataract skeletal anomalies, cennamo gangemi syndrome, cerebellar agenesis, cerebello-olivary atrophy, cerebral calcification cerebellar hypoplasia, cerebral calcifications opalescent teeth phosphaturia, oculo digital syndrome, chondrodysplasia, choreoacanthocytosis amyotrophic, chorioretinopathy dominant form microcephaly, Christian Demyer Franken syndrome, Christian Johnson angenieta syndrome, chromosome 3 duplication syndrome, chronic demyelinizing neuropathy with IgM monoclonal, ciliary dyskinesia-bronchiectasis, circumscribed cutaneous aplasia of the vertex, circumscribed disseminated keratosis Jadassohn lew type, cleft lip and palate malrotation cardiopathy, cleft lip and/or palate with mucous cysts of lower, cleft lip palate dysmorphism kumar type, cleft lip palate intellectual disability corneal opacity, cleft lip palate oligodontia syndactyly pili torti, cleft lip palate pituitary deficiency, cleft lip palate-tetraphocomelia, cleft lower lip cleft lateral canthi chorioretinal, cleft palate cardiac defect ectrodactyly, cleft palate colobomata radial synostosis deafness, cleft palate heart disease polydactyly absent tibia, cleft tongue, coarse face hypotonia constipation, Cohen Lockood Wyborney syndrome, type 2 collagenopathy, Collins-Sakati syndrome, coloboma porencephaly hydronephrosis, colobomata unilobar lung heart defect, colonic malakoplakia, Colver Steer Godman syndrome, Combarros Calleja Leno syndrome, complement receptor deficiency, congenital absence of the sternocleidomastoid muscle, congenital amputation, congenital aneurysms of the great vessels, congenital articular rigidity, congenital benign spinal muscular atrophy dominant, congenital cardiovascular shunt, congenital contractures, congenital craniosynostosis maternal hyperthyroiditis, congenital cystic eye, congenital heart disease ptosis hypodontia craniostosis, congenital heart disease radio ulnar synostosis intellectual disability, congenital mumps, congenital stenosis of cervical medullary canal, Dennis-Fairhurst-Moore syndrome, congenital unilateral pulmonary hypoplasia, congenital vagal hyperreflexivity, Cormier Rustin Munnich syndrome, corneal crystals myopathy neuropathy, corneal dystrophy ichthyosis microcephaly intellectual disability, corneal dystrophy pigmentary anomaly malabsorption, corpus callosum agenesis of blepharophimosis robin type, corpus callosum dysgenesis X-linked recessive, corpus callosum dysgenesis cleft spasm, corpus callosum dysgenesis hypopituitarism, cortada Koussef Matsumoto syndrome, Cortes Lacassie syndrome, craniofacial and skeletal defects, craniofacial dysostosis arthrogryposis progeroid appearance, craniofrontonasal syndrome Teebi type, craniostenosis with congenital heart disease intellectual disability, crawfurd syndrome, cutis gyratum acanthosis nigricans craniosynostosis, cutis laxa osteoporosis, Davenport-Donlan syndrome, Davis Lafer syndrome, de Hauwere Leroy adriaenssens syndrome, deafness conductive stapedial ear malformation facial palsy, deafness goiter stippled epiphyses, deafness hypospadias metacarpal and metatarsal syndrome, deafness mesenteric diverticula of small bowel neuropathy, deafness peripheral neuropathy arterial disease, deafness progressive cataract autosomal dominant, dermatocardioskeletal syndrome boronne type, dextrocardia with situs inversus, diabetes persistent mullerian ducts, diaphragmatic agenesis radial aplasia omphalocele, diaphragmatic hernia exomphalos corpus callosum agenesis, diaphragmatic hernia upper limb defects, die Smulders droog van dijk syndrome, diomedi bernardi placidi syndrome, diphallus rachischisis imperforate anus, distichiasis heart congenital anomalies, double discordia, double uterus-hemivagina-renal agenesis, Drachtman Weinblatt Sitarz syndrome, Duker-Weiss-Siber syndrome, duodenal atresia tetralogy of fallot, duplication of leg mirror foot, duplication of the thumb unilateral biphalangeal, dupont sellier chochillon syndrome, dwarfism bluish sclerae, dwarfism deafness retinitis pigmentosa, dwarfism lethal type advanced bone age, dwarfism thin bones multiple fractures, dysmorphism cleft palate loose skin, Eagle syndrome, ectrodactyly cardiopathy dysmorphism, Elliott ludman Teebi syndrome, enamel hypoplasia cataract hydrocephaly, encephalocele anencephaly, enchondromatosis dwarfism deafness, Engelhard Yatziv syndrome, enlarged vestibular aqueduct syndrome, epidermal nevus vitamin D resistant rickets, epimetaphyseal dysplasia cataract, epiphyseal dysplasia dysmorphism camptodactyly, esophageal atresia coloboma talipes, extrasystoles short stature hyperpigmentation microcephaly, facial clefting corpus callosum agenesis, facio digito genital syndrome recessive form, facio skeletal genital syndrome rippberger type, familial capillaro-venous leptomeningeal angiomatosis, Dursun syndrome, Faye-Petersen-Ward-Carey syndrome, feigenbaum Bergeron syndrome, Feingold trainer syndrome, fetal brain disruption sequence, fetal enterovirus syndrome, fetal parainfluenza virus type 3 syndrome, fetal phenothiazine syndrome, fibromatosis multiple non ossifying, fibula aplasia complex brachydactyly, fibular hypoplasia scapulo pelvic dysplasia absent, Fitz-Hugh-Curtis syndrome, focal alopecia congenital megalencephaly, focal or multifocal malformations in neuronal migration, foix chavany Marie syndrome, Fontaine farriaux blanckaert syndrome, Fraser Jequier Chen syndrome, Freiberg disease, Friedman Goodman syndrome, frontonasal malformation cloacal exstrophy, frontonasal dysplasia Klippel feil syndrome, frontonasal dysplasia phocomelic upper limbs, Fryns Fabry Remans syndrome, Fryns Smeets Thiry syndrome, Fuchs atrophia gyrata chorioideae et retinae, Fukuda-Miyanomae-Nakata syndrome, Fuqua Berkovitz syndrome, Garret-Tripp syndrome, gas bloat syndrome, Gaucher ichthyosis restrictive dermopathy, gershinibaruch Leibo syndrome, Ghose-Sachdev-Kumar syndrome, gigantism advanced bone age hoarse cry, glossopalatine ankylosis micrognathia ear anomalies, goldstein hutt syndrome, goniodysgenesis intellectual disability short stature, green sandford davison syndrome, grix Blankenship Peterson syndrome, Ho-Kaufman-McAlister syndrome, Jaffer-Beighton syndrome, Judge Misch wright syndrome, Kashani-Strom-Utley syndrome, Kasznica-Carlson-Coppedge syndrome, Katsantoni-Papadakou-Lagoyanni syndrome, Kocher-debre-Semelaigne syndrome, Koone-Rizzo-Elias syndrome, Kozlowski Brown Hardwick syndrome, Kozlowski Ouvrier syndrome, Kozlowski Rafinski Klicharska syndrome, Kozlowski Warren Fisher syndrome, Krauss Herman Holmes syndrome, Krieble Bixler syndrome, Kuster Majewski Hammerstein syndrome, Kuster syndrome, Laugier-Hunziker syndrome, Laurence-Prosser-Rocker syndrome, le Marec-Bracq-Picaud syndrome, levator syndrome, Marinesco-Sjogren-like syndrome, Milner-Khallouf-Gibson syndrome, radio-digito-facial dysplasia, Seckel like syndrome majoor-krakauer type, neonatal aspiration syndrome, muscular fibrosis multifocal obstructed vessels, short stature contractures hypotonia, Alice in Wonderland syndrome, megacystis-microcolon-intestinal hypoperistalsis syndrome, Basilicata-Akhtar syndrome, Liberfarb syndrome, craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome, cardiac, facial, and digital anomalies with developmental delay, fibrosis, neurodegeneration, and cerebral angiomatosis, Duane anomaly-myopathy-scoliosis syndrome, congenital cataract-severe neonatal hepatopathy-global developmental delay syndrome, infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome, acute radiation syndrome, monoclonal mast cell activation syndrome, oculocerebrodental syndrome, syndromic congenital sodium diarrhea, congenital brachyesophagus-intrathoracic stomach-vertebral anomalies syndrome, intellectual disability-cardiac anomalies-short stature-joint laxity syndrome, intrauterine growth restriction-congenital multiple café-au-lait macules-increased sister chromatid exchange syndrome, frontonasal dysplasia-bifid nose-upper limb anomalies syndrome, microcephaly-facial dysmorphism-ocular anomalies-multiple congenital anomalies syndrome, diaphragmatic hernia-short bowel-asplenia syndrome, warts-immunodeficiency-lymphedema-anogenital dysplasia syndrome, Cramp-fasciculation syndrome, choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome, blepharophimosis-intellectual disability syndrome/genitopatellar overlap syndrome, CCNK-related neurodevelopmental disorder-severe intellectual disability-facial dysmorphism syndrome, cerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndrome, KLHL7-related Bohring-Opitz-like syndrome, KLHL7-related cold-induced sweating-like syndrome, KAT6B-related multiple congenital anomalies syndrome, oculogastrointestinal-neurodevelopmental syndrome, spastic paraparesis-cataracts-speech delay syndrome, Ruzicka-Goerz-Anton syndrome, Sammartino-Decreccio syndrome, Samson-Gardner syndrome, Samson-Viljoen syndrome, Sanderson-Fraser syndrome, Sandhaus-Ben-Ami syndrome, prostatic malacoplakia associated with prostatic abscess, Saul-Wilkes-Stevenson syndrome, macrogyria, pseudobulbar palsy and intellectual disability, Schwartz-Cohen-addad-Lambert syndrome, Schlegelberger-Grote syndrome, Schrander-stumpel-Theunissen-Hulsmans syndrome, Saal-Bulas syndrome, Sackey-Sakati-Aur syndrome, Slti-Salem syndrome, Zerres Rietschel Majewski syndrome, Zazam Sheriff Phillips syndrome, Zadik-Barak-Levin syndrome, weinstein kliman scully syndrome, thickened earlobes with conductive deafness from incus-stapes abnormalities, ichthyosis linearis circumflexa, infantile striato thalamic degeneration, Landy-Donnai syndrome, merlob grunebaum reisner syndrome, Pavone Fiumara Rizzo syndrome, pfeiffer rockelein syndrome, Pfeiffer Tietze Welte syndrome, phosphoribosylpyrophosphate synthetase deficiency, piepkorn karp hickok syndrome, podder-tolmie syndrome, pointer syndrome, richieri-costa guion-almeida cohen syndrome, Rubinstein Taybi like syndrome, ruvalcaba churesigaew myhre syndrome, short limb dwarf lethal colavita kozlowski type, Mallory-Weiss syndrome, superior vena cava syndrome, piriformis syndrome, engraftment syndrome, Adams-Stokes syndrome, Leriche syndrome, multiple organ dysfunction syndrome, posterior leukoencephalopathy syndrome, cardio-renal syndrome, Rahman syndrome, X-linked keloid scarring-reduced joint mobility-increased optic cup-to-disc ratio syndrome, retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome, congenital labioscrotal agenesis-cerebellar malformation-corneal dystrophy-facial dysmorphism syndrome, Lopes-Maciel-Rodan syndrome, Stankiewicz-Isidor syndrome, Skraban-Deardorff syndrome, joint laxity, short stature, and myopia, Sweeney-Cox syndrome, Alkuraya-Kucinskas syndrome, Jaberi-Elahi syndrome, neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures, hearing impairment and infertile male syndrome, cardiocutaneous syndrome, neonatal diabetes, congenital sensorineural hearing loss and congenital cataracts, cardioectodermal syndrome, cannabinoid hyperemesis syndrome, retrograde cricopharyngeus dysfunction, Zinner syndrome, retinal dystrophy-ataxia-pituitary hormone abnormality-hypogonadism syndrome, IFAP syndrome, DICER1-related tumor predisposition, Roberts-SC phocomelia syndrome, carcinoid syndrome, Bonnevie-Ullrich syndrome, NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction, RNU4ATAC spectrum disorder, syndromic congenital heart disease, hand-foot syndrome, central hypoventilation syndrome, congenital, 1, with or without Hirschsprung disease, gastrointestinal defects and immunodeficiency syndrome 1, achalasia-alacrima syndrome, black locks with albinism and deafness syndrome, Birt-Hogg-Dube syndrome, trigeminal trophic syndrome, developmental and/or epileptic encephalopathy with spike-wave activation in sleep, syndromic microspherophakia, painful legs and moving toes syndrome, congenital aphakia-iris hypoplasia-microphthalmia-microcornea syndrome, hereditary persistence of fetal hemoglobin-intellectual disability syndrome, developmental delay-immunodeficiency-leukoencephalopathy-hypohomocysteinemia syndrome, primary hypomagnesemia-generalized seizures-intellectual disability-obesity syndrome, post-cardiac arrest syndrome, early-onset obesity-hyperphagia-severe developmental delay syndrome, hereditary alpha tryptasemia syndrome, KINSSHIP syndrome, developmental delay, hypotrophy, and dysmorphic features without moebius syndrome, breast implant illness, cataracts, hearing impairment, nephrotic syndrome, and enterocolitis, craniosynostosis-facial dysmorphism-chiari-1 malformation-developmental and language delay syndrome, MYT1L-related developmental delay-intellectual disability-obesity syndrome, Houge-Janssens syndrome, xerosis and growth failure with immune and pulmonary dysfunction syndrome, Fliedner-Zweier syndrome, Lui-Jee-Baron syndrome, Long-Olsen-Distelmaier syndrome, Tan-Almurshedi syndrome, diabetes, deafness, developmental delay, and short stature syndrome, Alfadhel syndrome, Hoxha-Aliu syndrome, cleft palate-congenital heart defect-intellectual disability syndrome, congenital insensitivity to pain syndrome, Marsili type, Yuksel-Vogel-Bauer syndrome, polydactyly-macrocephaly syndrome, pyoderma gangrenosum-acne-hidradenitis suppurativa-ankylosing spondylitis syndrome, psoriatic arthritis-pyoderma gangrenosum-acne-hidradenitis suppurativa syndrome, megalencephaly-polydactyly syndrome, Leigh syndrome, mitochondrial, auroneurodental syndrome, orofacial clefting-cardiac anomalies-facial dysmorphism syndrome, Grisel syndrome, arterial tortuosity-bone fragility syndrome, dialysis disequilibrium syndrome, brain abnormalities-severe developmental delay-facial dysmorphism-intellectual disability syndrome due to MEF2C mutation, Kariminejad neurodevelopmental syndrome, myelofibrosis, congenital, with anemia, neutropenia, developmental delay, and ocular abnormalities, brain malformation renal syndrome, myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis 2, Karayol-Borroto-Haghshenas neurodevelopmental syndrome, neurodegeneration, infantile-onset, with optic atrophy and brain abnormalities, Morimoto-Ryu-Malicdan neuromuscular syndrome, neurodevelopmental disorder with dysmorphic facies, absent speech and ambulation, and brain abnormalities, neurodevelopmental disorder with variable familial hypercholanemia, Pan-Chung-Bellen syndrome, telangiectasia, impaired intellectual development, microcephaly, metaphyseal dysplasia, eye abnormalities, and short stature, Muggenthaler-Chowdhury-Chioza syndrome, Tayoun-Maawali syndrome, ragopathy, cardiovascular-kidney-metabolic syndrome, craniofaciocardiohepatic syndrome, FICUS syndrome, Li-Takada-Miyake syndrome, Guillouet-Gordon syndrome, ICHAD syndrome, cataract, alopecia, oral mucosal disorder, and psoriasis-like syndrome, RAC2-related combined immunodeficiency-bronchiectasis-cancer-predisposing syndrome, oculovertebral syndrome, Alsahan-Harris syndrome, Ververi-Brady syndrome, Dursun-Ozgul neurodevelopmental syndrome, immune dysregulation, neurodevelopmental defects, and colitis, Harel-Tora neurodevelopmental syndrome, Valence-Farazi cerebellar ataxia syndrome, dyschromatosis, ichthyosis, deafness, and atopic disease, Ramond-Elliott neurodevelopmental syndrome, STAD syndrome, craniosynostosis-scoliosis syndrome, loin pain hematuria syndrome, IRF6-related condition, linkeropathy, NDUFB11-related disorders, CRYAB-related myofibrillar myopathy-cataract-cardiomyopathy spectrum disorder, TSEN2-related neurodevelopmental disorder with or without thrombotic microangiopathy, antiphospholipid syndrome

Genetics & variants

GWAS landscape

79 GWAS associations across 17 studies. Top hits map to 23 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs9266490	2e-44	RNU6-283P - FGFR3P1	G	2.73
HLA-B*51	7e-32		?	3.82
rs4959053	2e-20	PSORS1C1	?	4.38
rs1518111	4e-18	IL19, IL10	?	1.45
rs1800871	1e-14	IL19, IL10	T	1.45
rs7616215	4e-13	CCR3	C	1.39
rs76830965	3e-12	IL12A-AS1	A	1.66
rs4947296	1e-11	RNU6-1133P - C6orf15	?	2.57
rs1495965	2e-11	DNAJB6P4 - IL12RB2	G	1.35
rs17482078	5e-11	ERAP1	T	4.56
rs17810546	1e-10	IL12A-AS1	G	1.66
rs6660226	1e-10	DNAJB6P4 - IL12RB2	A	0.79
rs9266406	2e-10	HLA-B - RNU6-283P	?	2.29
rs2848479	3e-10	LINC02713 - CNTN5	A	1.66
rs3024490	3e-10	IL10, IL19	A	1.26
rs9357105	6e-10	MUC22 - HCG22	?
rs2087726	9e-10	CCR3	G	0.79
rs7574070	1e-09	STAT4	A	1.27
rs2617170	1e-09	KLRC4-KLRK1, KLRC4	T	1.28
rs4896243	2e-09	IL22RA2 - IFNGR1	C	1.25
rs17006292	5e-09	TFCP2L1	?	4.17
rs681343	5e-09	FUT2	T	1.3
rs142459005	5e-09	HLA-B	?
rs897200	6e-09	STAT4	A	1.45
rs4143322	6e-09	RN7SKP101 - SEMA6D	?
rs924080	7e-09	DNAJB6P4 - IL12RB2	?	1.28
rs2121034	9e-09	LACC1 - NRAD1	T	0.79
rs74566205	1e-08	NPHP4	?
rs1874886	2e-08	IL12A-AS1	A	1.61
rs1660760	3e-08	RPL31P44 - THAP12P3	T	0.78

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST012073	Ortiz Fernandez L	2021	2,344	1,920	Genetic association of a gain of function interferon gamma receptor 1 (IFNGR1) polymorphism and the intergenic region LNCAROD/DKK1 with Behçet’s disease.
GCST90448092	Jung ES	2023	1,689	2,327	Genome-wide association analysis reveals the associations of NPHP4, TYW1-AUTS2 and SEMA6D for Behçet’s disease and HLA-B*46:01 for its intestinal involvement.
GCST000726	Remmers EF	2010	1,215	1,278	Genome-wide association study identifies variants in the MHC class I, IL10, and IL23R-IL12RB2 regions associated with Behçet’s disease.
GCST000728	Mizuki N	2010	611	0	Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behçet’s disease susceptibility loci.
GCST001804	Kirino Y	2013	435	1,278	Genome-wide association analysis identifies new susceptibility loci for Behçet’s disease and epistasis between HLA-B*51 and ERAP1.
GCST001707	Lee YJ	2012	367	0	Genome-wide association study identifies GIMAP as a novel susceptibility locus for Behcet’s disease.
GCST009887	Xavier JM	2013	292	0	FUT2: filling the gap between genes and environment in Behçet’s disease?
GCST90448093	Jung ES	2023	279	0	Genome-wide association analysis reveals the associations of NPHP4, TYW1-AUTS2 and SEMA6D for Behçet’s disease and HLA-B*46:01 for its intestinal involvement.
GCST007551	Ortiz-Fernandez L	2016	278	1,517	Genetic Analysis with the Immunochip Platform in Behçet Disease. Identification of Residues Associated in the HLA Class I Region and New Susceptibility Loci.
GCST90651989	Liu TY	2025	253	215,661	Diversity and longitudinal records: Genetic architecture of disease associations and polygenic risk in the Taiwanese Han population.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	3
Tier 2: splice/UTR	0
Tier 3: regulatory	2
Tier 4: intronic/intergenic	45

MAF distribution

Bucket	Variants
common (>=0.05)	48
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intron_variant	29
intergenic_variant	13
missense_variant	2
unknown	1
stop_gained	1
non_coding_transcript_exon_variant	1
regulatory_region_variant	1
intron_variant; intron_variant; regulatory_region_variant	1
synonymous_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs9266490	6	31372381	A>C,G	0.279	intron_variant	RNU6-283P - FGFR3P1	2e-44	Tier 4: intronic/intergenic
HLA-B*51				0.079			7e-32	Tier 4: intronic/intergenic
rs4959053	6	31131800	G>A	0.11	intron_variant	PSORS1C1	2e-20	Tier 4: intronic/intergenic
rs1518111	1	206771300	T>A,C,G	0.05	intron_variant	IL19, IL10	4e-18	Tier 4: intronic/intergenic
rs1800871	1	206773289	A>C,G,T	0.31	intron_variant	IL19, IL10	1e-14	Tier 4: intronic/intergenic
rs7616215	3	46164194	C>G,T	0.346	intron_variant	CCR3	4e-13	Tier 4: intronic/intergenic
rs76830965	3	159919889	C>A,G,T	0.05	intron_variant	IL12A-AS1	3e-12	Tier 4: intronic/intergenic
rs4947296	6	31090401	T>A,C	0.05	intergenic_variant	RNU6-1133P - C6orf15	1e-11	Tier 4: intronic/intergenic
rs1495965	1	67287825	C>A,T	0.49	intergenic_variant	DNAJB6P4 - IL12RB2	2e-11	Tier 4: intronic/intergenic
rs17482078	5	96783162	C>G,T	0.02	missense_variant	ERAP1	5e-11	Tier 1: coding
rs17810546	3	159947262	A>G	0.05	intron_variant	IL12A-AS1	1e-10	Tier 4: intronic/intergenic
rs6660226	1	67278918	G>A,T	0.05	intergenic_variant	DNAJB6P4 - IL12RB2	1e-10	Tier 4: intronic/intergenic
rs9266406	6	31368641	G>A,T	0.4	intron_variant	HLA-B - RNU6-283P	2e-10	Tier 4: intronic/intergenic
rs2848479	11	98216871	C>T	0.401	intergenic_variant	LINC02713 - CNTN5	3e-10	Tier 4: intronic/intergenic
rs3024490	1	206771966	A>C,G,T	0.05	intron_variant	IL10, IL19	3e-10	Tier 4: intronic/intergenic
rs9357105	6	31036146	G>A	0.05	intergenic_variant	MUC22 - HCG22	6e-10	Tier 4: intronic/intergenic
rs2087726	3	46166818	G>A	0.05	intron_variant	CCR3	9e-10	Tier 4: intronic/intergenic
rs7574070	2	191145762	A>C	0.421	intron_variant	STAT4	1e-09	Tier 4: intronic/intergenic
rs2617170	12	10408358	T>C	0.37	missense_variant	KLRC4-KLRK1, KLRC4	1e-09	Tier 1: coding
rs4896243	6	137193653	C>T	0.05	intergenic_variant	IL22RA2 - IFNGR1	2e-09	Tier 4: intronic/intergenic
rs17006292	2	121261187	C>A,T	0.075	intron_variant	TFCP2L1	5e-09	Tier 4: intronic/intergenic
rs681343	19	48703205	C>A,T	0.435	stop_gained	FUT2	5e-09	Tier 1: coding
rs142459005	6	31361146	A>C,T	0.05	non_coding_transcript_exon_variant	HLA-B	5e-09	Tier 4: intronic/intergenic
rs897200	2	191153045	T>C,G	0.471	regulatory_region_variant	STAT4	6e-09	Tier 3: regulatory
rs4143322	15	46858709	T>C,G	0.05	intergenic_variant	RN7SKP101 - SEMA6D	6e-09	Tier 4: intronic/intergenic
rs924080	1	67294457	T>C	0.05	intergenic_variant	DNAJB6P4 - IL12RB2	7e-09	Tier 4: intronic/intergenic
rs2121034	13	43899730	G>A,C,T	0.05	intron_variant	LACC1 - NRAD1	9e-09	Tier 4: intronic/intergenic
rs74566205	1	5977548	C>T	0.05	intron_variant	NPHP4	1e-08	Tier 4: intronic/intergenic
rs1874886	3	160011868	G>A	0.37	intron_variant	IL12A-AS1	2e-08	Tier 4: intronic/intergenic
rs1660760	10	52394860	T>A,C,G	0.05	intergenic_variant	RPL31P44 - THAP12P3	3e-08	Tier 4: intronic/intergenic

ClinVar germline variants

22 retrieved; paginated sample, class counts are floors:

5 pathogenic, 5 uncertain significance, 4 association, 3 conflicting classifications of pathogenicity, 3 benign/likely benign, 1 likely benign, 1 benign; association

ClinVar	Variant (HGVS)	Gene	Classification	Review
430715	NM_000243.3(MEFV):c.332G>A (p.Gly111Glu)	MEFV	Pathogenic	no assertion criteria provided
267317	NM_022162.2(NOD2):c.2446G>A	NOD2	Pathogenic	no assertion criteria provided
267319	NM_022162.2(NOD2):c.2197G>T (p.Val733Leu)	NOD2	Pathogenic	no assertion criteria provided
268134	NM_001370466.1(NOD2):c.964C>T (p.Leu322Phe)	NOD2	Pathogenic	no assertion criteria provided
267318	NM_001065.3(TNFRSF1A):c.463C>T (p.His155Tyr)	TNFRSF1A	Pathogenic	no assertion criteria provided
375253	NM_000243.3(MEFV):c.1099C>G (p.Leu367Val)	MEFV	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
234423	NM_001065.4(TNFRSF1A):c.596T>C (p.Ile199Thr)	TNFRSF1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
378735	NM_001065.4(TNFRSF1A):c.935G>A (p.Arg312Lys)	TNFRSF1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
375246	NM_001282225.2(ADA2):c.145C>T (p.Arg49Trp)	ADA2	Uncertain significance	criteria provided, multiple submitters, no conflicts
375251	NM_001282225.2(ADA2):c.740C>T (p.Ala247Val)	ADA2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1321243	NM_001145306.2(CDK6):c.647+21377A>G	CDK6	association	no assertion criteria provided
1321244	NM_001145306.2(CDK6):c.*5310T>C	CDK6	association	no assertion criteria provided
916545	NM_003855.5(IL18R1):c.-29+2476T>G	IL18R1	association	criteria provided, single submitter
916547	NM_003855.5(IL18R1):c.59-1038C>A	IL18R1	association	criteria provided, single submitter
375252	NM_000243.3(MEFV):c.1211A>G (p.His404Arg)	MEFV	Uncertain significance	criteria provided, multiple submitters, no conflicts
280941	NM_003978.5(PSTPIP1):c.364G>A (p.Val122Ile)	PSTPIP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
280942	NM_003978.5(PSTPIP1):c.865G>C (p.Asp289His)	PSTPIP1	Uncertain significance	criteria provided, single submitter
375247	NM_001282225.2(ADA2):c.927G>A (p.Met309Ile)	ADA2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
430693	NM_001282225.2(ADA2):c.1045G>A (p.Val349Ile)	ADA2	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
916546	NM_003855.5(IL18R1):c.-29+1269C>T	IL18R1	Benign; association	criteria provided, multiple submitters, no conflicts
267320	NM_022162.2(NOD2):c.241C>G (p.Leu81Val)	NOD2	Likely benign	criteria provided, multiple submitters, no conflicts
317171	NM_003978.5(PSTPIP1):c.203C>T (p.Thr68Met)	PSTPIP1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 52 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
STAT4	Orphanet:117	Behçet disease
STAT4	Orphanet:536	Systemic lupus erythematosus
STAT4	Orphanet:85408	Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
STAT4	Orphanet:85410	Oligoarticular juvenile idiopathic arthritis
STAT4	Orphanet:93552	Pediatric systemic lupus erythematosus
TNFRSF1A	Orphanet:32960	Tumor necrosis factor receptor 1 associated periodic syndrome
TNFRSF1A	Orphanet:329967	Intermittent hydrarthrosis
TNFSF15	Orphanet:186	Primary biliary cholangitis
CCR1	Orphanet:117	Behçet disease
PARK7	Orphanet:2828	Young-onset Parkinson disease
PARK7	Orphanet:90020	Parkinson-dementia complex of Guam
CDK6	Orphanet:2512	Autosomal recessive primary microcephaly
ERAP1	Orphanet:117	Behçet disease
ADA2	Orphanet:124	Diamond-Blackfan anemia
ADA2	Orphanet:404553	Deficiency of adenosine deaminase 2
ADA2	Orphanet:820	Sneddon syndrome
IL23R	Orphanet:117	Behçet disease
UBAC2	Orphanet:117	Behçet disease
CPLX1	Orphanet:280	Wolf-Hirschhorn syndrome
CPLX1	Orphanet:352582	Familial infantile myoclonic epilepsy
NSMCE2	Orphanet:436182	Microcephalic primordial dwarfism-insulin resistance syndrome
NSMCE2	Orphanet:808	Seckel syndrome
LACC1	Orphanet:85414	Systemic-onset juvenile idiopathic arthritis
IL12A-AS1	Orphanet:117	Behçet disease
HLA-B	Orphanet:117	Behçet disease
HLA-B	Orphanet:275798	Pulmonary arterial hypertension associated with connective tissue disease
HLA-B	Orphanet:29207	Reactive arthritis
HLA-B	Orphanet:3287	Takayasu arteritis
HLA-B	Orphanet:36426	Stevens-Johnson syndrome
HLA-B	Orphanet:397	Giant cell arteritis
NOD2	Orphanet:90340	Blau syndrome
IRF8	Orphanet:319600	Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency
IFNGR1	Orphanet:117	Behçet disease
IFNGR1	Orphanet:319569	Autosomal recessive mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency
IFNGR1	Orphanet:319581	Autosomal dominant mendelian susceptibility to mycobacterial diseases due to partial IFNgammaR1 deficiency
IFNGR1	Orphanet:99898	Mendelian susceptibility to mycobacterial diseases due to complete IFNgammaR1 deficiency
IL10	Orphanet:117	Behçet disease
IL10	Orphanet:238569	Immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections syndrome
IL10	Orphanet:536	Systemic lupus erythematosus
IL12A	Orphanet:117	Behçet disease
IL12A	Orphanet:186	Primary biliary cholangitis
IRF5	Orphanet:186	Primary biliary cholangitis
IRF5	Orphanet:220393	Diffuse cutaneous systemic sclerosis
IRF5	Orphanet:220402	Limited cutaneous systemic sclerosis
IRF5	Orphanet:536	Systemic lupus erythematosus
KLRC4	Orphanet:117	Behçet disease
MEFV	Orphanet:117	Behçet disease
MEFV	Orphanet:3243	Sweet syndrome
MEFV	Orphanet:329967	Intermittent hydrarthrosis
MEFV	Orphanet:342	Familial Mediterranean fever

Cohort genes → proteins

43 cohort genes, 41 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	36
multi_evidence	7

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
STAT4	HGNC:11365	ENSG00000138378	Q14765	Signal transducer and activator of transcription 4	gwas
TNFRSF1A	HGNC:11916	ENSG00000067182	P19438	Tumor necrosis factor receptor superfamily member 1A	clinvar
TNFSF15	HGNC:11931	ENSG00000181634	O95150	Tumor necrosis factor ligand superfamily member 15	gwas
GUSBP1	HGNC:13670	ENSG00000183666	Q15486	Putative inactive beta-glucuronidase-like protein SMA3	gwas
CCR1	HGNC:1602	ENSG00000163823	P32246	C-C chemokine receptor type 1	gwas
CCR3	HGNC:1604	ENSG00000183625	P51677	C-C chemokine receptor type 3	gwas
PARK7	HGNC:16369	ENSG00000116288	Q99497	Parkinson disease protein 7	gwas
PSORS1C1	HGNC:17202	ENSG00000204540	Q9UIG5	Psoriasis susceptibility 1 candidate gene 1 protein	gwas
CDK6	HGNC:1777	ENSG00000105810	Q00534	Cyclin-dependent kinase 6	clinvar
TFCP2L1	HGNC:17925	ENSG00000115112	Q9NZI6	Transcription factor CP2-like protein 1	gwas
ERAP1	HGNC:18173	ENSG00000164307	Q9NZ08	Endoplasmic reticulum aminopeptidase 1	gwas
ADA2	HGNC:1839	ENSG00000093072	Q9NZK5	Adenosine deaminase 2	clinvar
IL23R	HGNC:19100	ENSG00000162594	Q5VWK5	Interleukin-23 receptor	gwas
THADA	HGNC:19217	ENSG00000115970	Q6YHU6	tRNA (32-2’-O)-methyltransferase regulator THADA	gwas
UBAC2	HGNC:20486	ENSG00000134882	Q8NBM4	Ubiquitin-associated domain-containing protein 2	gwas
CNTN5	HGNC:2175	ENSG00000149972	O94779	Contactin-5	gwas
CPLX1	HGNC:2309	ENSG00000168993	O14810	Complexin-1	gwas
ADO	HGNC:23506	ENSG00000181915	Q96SZ5	2-aminoethanethiol dioxygenase	gwas
CCDC71	HGNC:25760	ENSG00000177352	Q8IV32	Coiled-coil domain-containing protein 71	gwas
NSMCE2	HGNC:26513	ENSG00000156831	Q96MF7	E3 SUMO-protein ligase NSE2	gwas
LACC1	HGNC:26789	ENSG00000179630	Q8IV20	Purine nucleoside phosphorylase LACC1	gwas
HCG22	HGNC:27780	ENSG00000228789	E2RYF7	Protein PBMUCL2	gwas
HORMAD2	HGNC:28383	ENSG00000176635	Q8N7B1	HORMA domain-containing protein 2	gwas
DHFRP2	HGNC:2863	ENSG00000228432		dihydrofolate reductase pseudogene 2	gwas
FUT2	HGNC:4013	ENSG00000176920	Q10981	Galactoside alpha-(1,2)-fucosyltransferase 2	gwas
IL12A-AS1	HGNC:49094	ENSG00000244040		IL12A antisense RNA 1	gwas
HLA-B	HGNC:4932	ENSG00000234745	P01889	HLA class I histocompatibility antigen, B alpha chain	gwas
NOD2	HGNC:5331	ENSG00000167207	Q9HC29	Nucleotide-binding oligomerization domain-containing protein 2	clinvar
IRF8	HGNC:5358	ENSG00000140968	Q02556	Interferon regulatory factor 8	gwas
IFNGR1	HGNC:5439	ENSG00000027697	P15260	Interferon gamma receptor 1	gwas
IL10	HGNC:5962	ENSG00000136634	P22301	Interleukin-10	gwas
IL12A	HGNC:5969	ENSG00000168811	P29459	Interleukin-12 subunit alpha	gwas
IL12RB2	HGNC:5972	ENSG00000081985	Q99665	Interleukin-12 receptor subunit beta-2	gwas
IL18R1	HGNC:5988	ENSG00000115604	Q13478	Interleukin-18 receptor 1	clinvar
IRF5	HGNC:6120	ENSG00000128604	Q13568	Interferon regulatory factor 5	gwas
JRKL	HGNC:6200	ENSG00000183340	Q9Y4A0	Jerky protein homolog-like	gwas
KLRC4	HGNC:6377	ENSG00000183542	O43908	NKG2-F type II integral membrane protein	gwas
MEFV	HGNC:6998	ENSG00000103313	O15553	Pyrin	clinvar
MICA	HGNC:7090	ENSG00000204520	Q29983	MHC class I polypeptide-related sequence A	gwas
MICB	HGNC:7091	ENSG00000204516	Q29980	MHC class I polypeptide-related sequence B	gwas
ARRB2	HGNC:712	ENSG00000141480	P32121	Beta-arrestin-2	gwas
MTMR3	HGNC:7451	ENSG00000100330	Q13615	Phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR3	gwas
PSTPIP1	HGNC:9580	ENSG00000140368	O43586	Proline-serine-threonine phosphatase-interacting protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
STAT4	Signal transducer and activator of transcription 4	Transcriptional regulator mainly expressed in hematopoietic cells that plays a critical role in cellular growth, differentiation and immune response.
TNFRSF1A	Tumor necrosis factor receptor superfamily member 1A	Receptor for TNFSF2/TNF and homotrimeric TNFSF1/lymphotoxin-alpha.
TNFSF15	Tumor necrosis factor ligand superfamily member 15	Receptor for TNFRSF25 and TNFRSF6B.
CCR1	C-C chemokine receptor type 1	Chemokine receptor that plays a crucial role in regulating immune cell migration, inflammation, and immune responses.
CCR3	C-C chemokine receptor type 3	G protein-coupled receptor (GPCR) that plays a key role in the immune system by regulating the migration and activation of white blood cells in response to chemokines.
PARK7	Parkinson disease protein 7	Multifunctional protein with controversial molecular function which plays an important role in cell protection against oxidative stress and cell death acting as oxidative stress sensor and redox-sensitive chaperone and protease.
CDK6	Cyclin-dependent kinase 6	Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition.
TFCP2L1	Transcription factor CP2-like protein 1	Transcription factor that facilitates establishment and maintenance of pluripotency in embryonic stem cells (ESCs).
ERAP1	Endoplasmic reticulum aminopeptidase 1	Aminopeptidase that plays a central role in peptide trimming, a step required for the generation of most HLA class I-binding peptides.
ADA2	Adenosine deaminase 2	Adenosine deaminase that may contribute to the degradation of extracellular adenosine, a signaling molecule that controls a variety of cellular responses.
IL23R	Interleukin-23 receptor	Associates with IL12RB1 to form the interleukin-23 receptor.
THADA	tRNA (32-2’-O)-methyltransferase regulator THADA	Together with methyltransferase FTSJ1, methylates the 2’-O-ribose of nucleotides at position 32 of the anticodon loop of substrate tRNAs.
UBAC2	Ubiquitin-associated domain-containing protein 2	Restricts trafficking of FAF2 from the endoplasmic reticulum to lipid droplets.
CNTN5	Contactin-5	Contactins mediate cell surface interactions during nervous system development.
CPLX1	Complexin-1	Positively regulates a late step in exocytosis of various cytoplasmic vesicles, such as synaptic vesicles and other secretory vesicles.
ADO	2-aminoethanethiol dioxygenase	Plays a vital role in regulating thiol metabolism and preserving oxygen homeostasis by oxidizing the sulfur of cysteamine and N-terminal cysteine-containing proteins to their corresponding sulfinic acids using O2 as a cosubstrate.
NSMCE2	E3 SUMO-protein ligase NSE2	E3 SUMO-protein ligase component of the SMC5-SMC6 complex, a complex involved in DNA double-strand break repair by homologous recombination.
LACC1	Purine nucleoside phosphorylase LACC1	Purine nucleoside enzyme that catalyzes the phosphorolysis of adenosine, guanosine and inosine nucleosides, yielding D-ribose 1-phosphate and the respective free bases, adenine, guanine and hypoxanthine.
HORMAD2	HORMA domain-containing protein 2	Essential for synapsis surveillance during meiotic prophase via the recruitment of ATR activity.
FUT2	Galactoside alpha-(1,2)-fucosyltransferase 2	Catalyzes the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the terminal galactose on both O- and N-linked glycans chains of cell surface glycoproteins and glycolipids and the resulting epitope regulates several proc…
HLA-B	HLA class I histocompatibility antigen, B alpha chain	Antigen-presenting major histocompatibility complex class I (MHCI) molecule.
NOD2	Nucleotide-binding oligomerization domain-containing protein 2	Pattern recognition receptor (PRR) that detects bacterial peptidoglycan fragments and other danger signals and plays an important role in gastrointestinal immunity.
IRF8	Interferon regulatory factor 8	Transcription factor that specifically binds to the upstream regulatory region of type I interferon (IFN) and IFN-inducible MHC class I genes (the interferon consensus sequence (ICS)).
IFNGR1	Interferon gamma receptor 1	Receptor subunit for interferon gamma/INFG that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation.
IL10	Interleukin-10	Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation.
IL12A	Interleukin-12 subunit alpha	Heterodimerizes with IL12B to form the IL-12 cytokine or with EBI3/IL27B to form the IL-35 cytokine.
IL12RB2	Interleukin-12 receptor subunit beta-2	Receptor for interleukin-12.
IL18R1	Interleukin-18 receptor 1	Within the IL18 receptor complex, responsible for the binding of the pro-inflammatory cytokine IL18, but not IL1A nor IL1B.
IRF5	Interferon regulatory factor 5	Transcription factor that plays a critical role in innate immunity by activating expression of type I interferon (IFN) IFNA and INFB and inflammatory cytokines downstream of endolysosomal toll-like receptors TLR7, TLR8 and TLR9.
KLRC4	NKG2-F type II integral membrane protein	May play a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells.
MEFV	Pyrin	Involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma.
MICA	MHC class I polypeptide-related sequence A	Widely expressed membrane-bound protein which acts as a ligand to stimulate an activating receptor KLRK1/NKG2D, expressed on the surface of essentially all human natural killer (NK), gammadelta T and CD8 alphabeta T-cells.
MICB	MHC class I polypeptide-related sequence B	Widely expressed membrane-bound protein which acts as a ligand to stimulate an activating receptor KLRK1/NKG2D, expressed on the surface of essentially all human natural killer (NK), gammadelta T and CD8+ alphabeta T-cells.
ARRB2	Beta-arrestin-2	Functions in regulating agonist-mediated G-protein coupled receptor (GPCR) signaling by mediating both receptor desensitization and resensitization processes.
MTMR3	Phosphatidylinositol-3,5-bisphosphate 3-phosphatase MTMR3	Lipid phosphatase that specifically dephosphorylates the D-3 position of phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate, generating phosphatidylinositol and phosphatidylinositol 5-phosphate.
PSTPIP1	Proline-serine-threonine phosphatase-interacting protein 1	Involved in regulation of the actin cytoskeleton.

Protein-family classification

Druggable: 18 · Difficult: 6 · Unknown: 19 · Druggable fraction: 0.42

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	9	6.1×	1e-04
Phosphatase	1	1.9×	0.954
Enzyme (other)	4	1.1×	0.954
GPCR	2	1.1×	0.954
Transcription factor	5	1.0×	0.954
Protease	1	0.8×	0.954
Other/Unknown	19	0.8×	0.954
Kinase	1	0.6×	0.954
Scaffold/PPI	1	0.4×	0.954

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
STAT4	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf
TNFRSF1A	Other/Unknown	no		Death_dom, TNFR/NGFR_Cys_rich_reg, DEATH-like_dom_sf
TNFSF15	Other/Unknown	no		TNF_dom, TNF, Tumour_necrosis_fac-like_dom
GUSBP1	Antibody/Immunoglobulin	yes		Ig-like_fold, Beta-gal/glucu_dom_sf
CCR1	GPCR	yes		GPCR_Rhodpsn, Chemokine_rcpt, Chemokine_CCR1
CCR3	GPCR	yes		GPCR_Rhodpsn, Chemokine_rcpt, Chemokine_CCR3
PARK7	Enzyme (other)	yes	3.5.1.124	DJ-1/PfpI, DJ-1, Class_I_gatase-like
PSORS1C1	Other/Unknown	no		SEEK1
CDK6	Kinase	yes	2.7.11.22	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
TFCP2L1	Transcription factor	no		CP2, SAM/pointed_sf, TFCP2L1_SAM
ERAP1	Protease	yes	3.4.11.1	Peptidase_M1, Peptidase_M1_dom, ERAP1-like_C_dom
ADA2	Enzyme (other)	yes	3.5.4.4	A_deaminase_dom, Ado/ade_deaminase, ADGF
IL23R	Antibody/Immunoglobulin	yes		FN3_dom, Ig-like_fold, FN3_sf
THADA	Other/Unknown	no		ARM-type_fold, THADA/TRM732_DUF2428, tRNA_methyltransferase_THADA
UBAC2	Other/Unknown	no		UBA-like_sf, UBA, Rhomboid-like_sf
CNTN5	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, FN3_dom
CPLX1	Other/Unknown	no		Synaphin
ADO	Enzyme (other)	yes	1.13.11.19	RmlC_Cupin_sf, PCO/ADO, RmlC-like_jellyroll
CCDC71	Other/Unknown	no		Ccdc71/71L
NSMCE2	Transcription factor	no		Znf_MIZ, Znf_RING/FYVE/PHD, Nse2(Mms21)
LACC1	Other/Unknown	no		Cu_polyphenol_OxRdtase, Cytotoxic_necrot_fac-like_cat, Cu_polyphenol_OxRdtase_sf
HCG22	Other/Unknown	no		EZH_Inhibitor
HORMAD2	Other/Unknown	no		HORMA_dom, HORMA_dom_sf, HORMA_MeioticProgression
DHFRP2	Other/Unknown	no
FUT2	Enzyme (other)	yes	2.4.1.344	Glyco_trans_11
IL12A-AS1	Other/Unknown	no
HLA-B	Antibody/Immunoglobulin	yes		MHC_I_a_a1/a2, Ig/MHC_CS, Ig_C1-set
NOD2	Other/Unknown	no		CARD, Leu-rich_rpt, NACHT_NTPase
IRF8	Other/Unknown	no		Interferon_reg_fact_DNA-bd_dom, SMAD_FHA_dom_sf, SMAD-like_dom_sf
IFNGR1	Antibody/Immunoglobulin	yes		FN3_dom, Interferon_gamma_rcpt_asu, Ig-like_fold
IL10	Other/Unknown	no		IL-10, 4_helix_cytokine-like_core, IL-10_CS
IL12A	Other/Unknown	no		IL-12_alpha, 4_helix_cytokine-like_core, IL-12
IL12RB2	Antibody/Immunoglobulin	yes		Hematopoietin_rcpt_Gp130_CS, FN3_dom, IgC2-like_lig-bd
IL18R1	Antibody/Immunoglobulin	yes		TIR_dom, Ig_sub, IL-1_rcpt_I/II-typ
IRF5	Other/Unknown	no		Interferon_reg_fact_DNA-bd_dom, SMAD_FHA_dom_sf, SMAD-like_dom_sf
JRKL	Transcription factor	no		DDE_SF_endonuclease_dom, HTH_CenpB_DNA-bd_dom, HTH_Psq
KLRC4	Other/Unknown	no		C-type_lectin-like/link_sf, CTDL_fold, NKG2/CD94_NK_receptors
MEFV	Transcription factor	no		Znf_B-box, B30.2/SPRY, SPRY_dom
MICA	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig-like_dom, MHC_I-like_Ag-recog
MICB	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig-like_dom, MHC_I-like_Ag-recog
ARRB2	Other/Unknown	no		Arrestin, Arrestin-like_N, Arrestin-like_C
MTMR3	Phosphatase	yes	3.1.3.95	Znf_FYVE, Tyr_Pase_cat, Myotubularin-like_Pase_dom
PSTPIP1	Scaffold/PPI	no		FCH_dom, SH3_domain, AH/BAR_dom_sf

Expression context

Cohort genes with no expression data: 0.

34 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	43
unknown	0

Top tissues across cohort

Tissue	Cohort genes
monocyte	10
granulocyte	7
leukocyte	7
mononuclear cell	6
buccal mucosa cell	4
secondary oocyte	4
lower esophagus mucosa	4
gall bladder	3
blood	3
oocyte	3
adrenal tissue	3
male germ line stem cell (sensu Vertebrata) in testis	3
sperm	2
cartilage tissue	2
jejunal mucosa	2
bone marrow cell	2
left testis	2
right testis	2
testis	2
minor salivary gland	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STAT4	201	broad	marker	granulocyte, sperm, middle temporal gyrus
TNFRSF1A	292	ubiquitous	marker	tendon of biceps brachii, gall bladder, left uterine tube
TNFSF15	149	broad	marker	cartilage tissue, jejunal mucosa, duodenum
GUSBP1	205	ubiquitous	marker	sural nerve, buccal mucosa cell, bone marrow cell
CCR1	244	broad	marker	monocyte, mononuclear cell, leukocyte
CCR3	100	tissue_specific	yes	secondary oocyte, blood, oocyte
PARK7	294	ubiquitous	marker	adult organism, tibia, deltoid
PSORS1C1	124	ubiquitous	yes	left testis, right testis, testis
CDK6	262	ubiquitous	marker	adrenal tissue, trabecular bone tissue, pylorus
TFCP2L1	209	broad	marker	parotid gland, saliva-secreting gland, minor salivary gland
ERAP1	286	ubiquitous	marker	jejunal mucosa, rectum, monocyte
ADA2	254	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
IL23R	39	tissue_specific	marker	secondary oocyte, oocyte, adrenal tissue
THADA	276	ubiquitous	marker	calcaneal tendon, right uterine tube, right lobe of thyroid gland
UBAC2	238	ubiquitous	marker	lower esophagus mucosa, upper arm skin, skin of abdomen
CNTN5	130	broad	marker	adrenal tissue, primordial germ cell in gonad, islet of Langerhans
CPLX1	187	broad	marker	lateral nuclear group of thalamus, lateral globus pallidus, postcentral gyrus
ADO	291	ubiquitous	yes	sperm, male germ cell, secondary oocyte
CCDC71	135	ubiquitous	yes	stromal cell of endometrium, thymus, fallopian tube
NSMCE2	259	ubiquitous	marker	colonic epithelium, bone marrow cell, tibialis anterior
LACC1	243	ubiquitous	marker	palpebral conjunctiva, corpus callosum, medial globus pallidus
HCG22	107	tissue_specific	yes	lower esophagus mucosa, male germ line stem cell (sensu Vertebrata) in testis, esophagus mucosa
HORMAD2	66	tissue_specific	marker	right testis, left testis, testis
DHFRP2	31	tissue_specific	yes	male germ line stem cell (sensu Vertebrata) in testis, cerebellar hemisphere, cerebellar cortex
FUT2	198	broad	marker	olfactory segment of nasal mucosa, nasal cavity epithelium, minor salivary gland
IL12A-AS1	144	tissue_specific	marker	lower esophagus mucosa, buccal mucosa cell, esophagus mucosa
HLA-B	134	ubiquitous	marker	blood, spleen, granulocyte
NOD2	189	broad	marker	monocyte, mononuclear cell, leukocyte
IRF8	265	broad	marker	monocyte, mononuclear cell, leukocyte
IFNGR1	295	ubiquitous	marker	lower lobe of lung, epithelium of nasopharynx, right lung

Protein interactions among cohort

Intra-cohort edges: 36.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDK6	6,767
IL10	6,185
PARK7	5,722
ARRB2	4,984
TNFRSF1A	4,523
IRF8	3,554
NOD2	3,527
HLA-B	3,209
CCR1	2,912
IRF5	2,737

Intra-cohort edges

A	B	Sources
ADO	IL23R	string_interaction
CCR1	CCR3	string_interaction
CCR1	KLRC4	string_interaction
CNTN5	JRKL	string_interaction
ERAP1	HLA-B	biogrid_interaction, intact, string_interaction
ERAP1	IL23R	string_interaction
ERAP1	KLRC4	string_interaction
ERAP1	TNFRSF1A	string_interaction
FUT2	KLRC4	string_interaction
HLA-B	PSORS1C1	string_interaction
HORMAD2	MTMR3	string_interaction
IFNGR1	TNFRSF1A	string_interaction
IL10	IL12A	string_interaction
IL10	IL12RB2	string_interaction
IL10	IL23R	string_interaction
IL10	IRF5	string_interaction
IL10	MTMR3	biogrid_interaction
IL12A	IL12RB2	string_interaction
IL12RB2	IL18R1	string_interaction
IL12RB2	KLRC4	string_interaction
IL12RB2	STAT4	biogrid_interaction, intact, string_interaction
IL18R1	TNFRSF1A	biogrid_interaction
IL23R	KLRC4	string_interaction
IL23R	NOD2	string_interaction
IL23R	STAT4	string_interaction
IRF5	IRF8	string_interaction
IRF5	STAT4	string_interaction
JRKL	KLRC4	string_interaction
KLRC4	STAT4	string_interaction
KLRC4	UBAC2	string_interaction
LACC1	NOD2	string_interaction
LACC1	TNFSF15	string_interaction
MEFV	PSTPIP1	intact, string_interaction
MICA	MICB	intact
NOD2	TNFSF15	string_interaction
TNFRSF1A	TNFSF15	string_interaction

Structural data

PDB: 26 · AlphaFold-only: 15 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HLA-B	P01889	237
PARK7	Q99497	88
ERAP1	Q9NZ08	23
CDK6	Q00534	22
TNFRSF1A	P19438	13
MEFV	O15553	11
MICA	Q29983	10
ADO	Q96SZ5	9
IL10	P22301	9
TNFSF15	O95150	7
IFNGR1	P15260	5
IL23R	Q5VWK5	4
IL12A	P29459	4
PSTPIP1	O43586	4
CCR1	P32246	3
NSMCE2	Q96MF7	3
IL18R1	Q13478	3
ADA2	Q9NZK5	2
THADA	Q6YHU6	2
CNTN5	O94779	2
CPLX1	O14810	2
IL12RB2	Q99665	2
MICB	Q29980	2
CCR3	P51677	1
IRF5	Q13568	1
ARRB2	P32121	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FUT2	Q10981	90.65
LACC1	Q8IV20	88.62
STAT4	Q14765	86.87
NOD2	Q9HC29	84.76
JRKL	Q9Y4A0	79.34
TFCP2L1	Q9NZI6	79.32
IRF8	Q02556	75.54
HORMAD2	Q8N7B1	72.61
UBAC2	Q8NBM4	72.34
HCG22	E2RYF7	69.41
MTMR3	Q13615	66.94
KLRC4	O43908	60.03
PSORS1C1	Q9UIG5	55.10
CCDC71	Q8IV32	52.59
GUSBP1	Q15486	50.13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 163. Enrichment computed across 43 evidence-associated genes (30 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 30 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Interleukin-35 Signalling	3	95.2×	6e-04	STAT4, IL12A, IL12RB2
Interleukin-10 signaling	4	31.1×	6e-04	TNFRSF1A, CCR1, IL10, IL12A
Interleukin-12 signaling	3	40.8×	0.003	STAT4, IL12A, IL12RB2
Interferon gamma signaling	4	16.7×	0.004	HLA-B, IRF8, IFNGR1, IRF5
Interleukin-23 signaling	2	84.6×	0.008	STAT4, IL23R
Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)	2	58.6×	0.014	STAT4, IL12RB2
Cytokine Signaling in Immune system	5	6.8×	0.017	STAT4, CCR1, IRF8, IFNGR1, IRF5
The NLRP3 inflammasome	2	44.8×	0.018	MEFV, PSTPIP1
Interferon alpha/beta signaling	3	15.2×	0.018	HLA-B, IRF8, IRF5
Immune System	8	3.5×	0.025	STAT4, CCR1, ADA2, IRF8, IFNGR1, IRF5, MEFV, MICB
Interferon Signaling	3	12.0×	0.029	IRF8, IFNGR1, IRF5
Purinergic signaling in leishmaniasis infection	2	28.2×	0.030	MEFV, PSTPIP1
TNFs bind their physiological receptors	2	26.2×	0.030	TNFRSF1A, TNFSF15
Antigen Presentation: Folding, assembly and peptide loading of class I MHC	2	26.2×	0.030	ERAP1, HLA-B
Interleukin-4 and Interleukin-13 signaling	3	10.3×	0.033	IL23R, IL10, IL12A
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	2	20.0×	0.045	STAT4, IL10
ABO blood group biosynthesis	1	190.3×	0.050	FUT2
Diseases of Cellular Senescence	1	126.9×	0.056	CDK6
Evasion of Oncogene Induced Senescence Due to p16INK4A Defects	1	126.9×	0.056	CDK6
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	1	126.9×	0.056	CDK6
Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects	1	126.9×	0.056	CDK6
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	1	126.9×	0.056	CDK6
Diseases of cellular response to stress	1	126.9×	0.056	CDK6
Chemokine receptors bind chemokines	2	12.5×	0.075	CCR1, CCR3
Drug-mediated inhibition of CDK4/CDK6 activity	1	76.1×	0.085	CDK6
TNFR1-mediated ceramide production	1	63.4×	0.095	TNFRSF1A
SLC15A4:TASL-dependent IRF5 activation	1	63.4×	0.095	IRF5
Interleukin-18 signaling	1	47.6×	0.113	IL18R1
IFNG signaling activates MAPKs	1	47.6×	0.113	IFNGR1
TGFBR3 regulates TGF-beta signaling	1	47.6×	0.113	ARRB2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 38 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
immune response	10	12.4×	2e-06	TNFSF15, CCR1, CCR3, HLA-B, IRF8, IL10, IL12A, IL18R1 (+2 more)
cytokine-mediated signaling pathway	7	24.1×	3e-06	STAT4, TNFRSF1A, CCR1, IL23R, IFNGR1, IL12RB2, IRF5
inflammatory response	10	9.9×	6e-06	TNFRSF1A, CCR1, CCR3, PARK7, IL23R, LACC1, IL18R1, IRF5 (+2 more)
positive regulation of type II interferon production	5	29.6×	8e-05	IL23R, IRF8, IL12A, IL12RB2, IL18R1
interleukin-12-mediated signaling pathway	3	147.8×	8e-05	STAT4, IL12A, IL12RB2
nucleotide-binding oligomerization domain containing 2 signaling pathway	3	121.0×	1e-04	LACC1, NOD2, IRF5
negative regulation of interleukin-12 production	3	83.2×	4e-04	IL10, MEFV, ARRB2
pattern recognition receptor signaling pathway	3	78.3×	4e-04	LACC1, NOD2, MEFV
positive regulation of cytokine production involved in immune response	3	78.3×	4e-04	LACC1, NOD2, IRF5
defense response to bacterium	5	14.2×	0.001	TNFRSF1A, NOD2, IRF8, IL10, MICA
positive regulation of NK T cell activation	2	177.4×	0.002	IL23R, IL12A
positive regulation of T cell mediated cytotoxicity	3	40.3×	0.002	IL23R, HLA-B, IL12A
cellular response to peptidoglycan	2	147.8×	0.003	NOD2, IRF5
adaptive immune response	5	11.1×	0.003	ERAP1, HLA-B, NOD2, IL18R1, MICB
positive regulation of interleukin-12 production	3	30.9×	0.004	IL23R, IRF8, IRF5
gamma-delta T cell activation	2	110.9×	0.004	MICA, MICB
cellular response to muramyl dipeptide	2	88.7×	0.006	NOD2, IRF5
T-helper 1 cell differentiation	2	80.6×	0.007	STAT4, IL18R1
cell surface receptor signaling pathway via JAK-STAT	3	22.9×	0.007	STAT4, TNFRSF1A, IL23R
detection of bacterium	2	73.9×	0.007	HLA-B, NOD2
negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway	2	68.2×	0.008	PARK7, IL10
defense response	3	17.1×	0.015	STAT4, HLA-B, NOD2
negative regulation of natural killer cell mediated cytotoxicity	2	46.7×	0.016	MICA, ARRB2
innate immune response	6	5.3×	0.016	LACC1, HLA-B, NOD2, IRF5, MEFV, PSTPIP1
cellular response to virus	3	15.8×	0.016	IFNGR1, IL12A, IRF5
positive regulation of acute inflammatory response to antigenic stimulus	1	443.5×	0.018	PARK7
negative regulation of chronic inflammatory response to antigenic stimulus	1	443.5×	0.018	IL10
detection of muramyl dipeptide	1	443.5×	0.018	NOD2
cellular response to glyoxal	1	443.5×	0.018	PARK7
glycolate biosynthetic process	1	443.5×	0.018	PARK7

Therapeutics

Drugs indicated or in trials for this disease

1 approved drug — disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Status
Apremilast	Approved (phase 4)

15 drugs in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Adalimumab	Phase 3
Cyclosporine	Phase 3
Gevokizumab	Phase 3
INTERFERON ALFA-2A	Phase 3
Infliximab	Phase 3
Secukinumab	Phase 3
Aldesleukin	Phase 2
Canakinumab	Phase 2
Colchicine	Phase 2
Dusquetide	Phase 2
Mufemilast	Phase 2
Pentoxifylline	Phase 2
Rituximab	Phase 2
Tocilizumab	Phase 2
Ustekinumab	Phase 2

Drug target analysis

Approved (phase 4): 3 · Phase ≥3: 3 · Phased (≥1): 7 · Undrugged: 36

Druggability breadth: 17 of 43 evidence-associated genes (40%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
CCR1	ABAMETAPIR
CDK6	PALBOCICLIB
NOD2	PACLITAXEL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CDK6	45	4
CCR1	8	4
NOD2	6	4
CCR3	2	2
ERAP1	2	2
TNFRSF1A	1	2
PARK7	1	2
STAT4	0	0
TNFSF15	0	0
GUSBP1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ABAMETAPIR	4	CCR1
RALTEGRAVIR	4	CCR1
PALBOCICLIB	4	CDK6
ABEMACICLIB	4	CDK6
RIBOCICLIB	4	CDK6
TRILACICLIB	4	CDK6
MOMELOTINIB	4	CDK6
SORAFENIB	4	CDK6
DABRAFENIB	4	CDK6
OLAPARIB	4	CDK6
PACLITAXEL	4	NOD2
DOCETAXEL ANHYDROUS	4	NOD2
GEFITINIB	4	NOD2
LEROCICLIB	3	CDK6
ALVOCIDIB	3	CDK6
DINACICLIB	3	CDK6
DALPICICLIB	3	CDK6
QUERCETIN	3	CDK6
DOVITINIB	3	CDK6
LESTAURTINIB	3	CDK6
METOCHALCONE	2	TNFRSF1A
AZD4818	2	CCR1
BX 471 FREE BASE	2	CCR1
BMS-817399	2	CCR1
CCX354	2	CCR1
BX 471	2	CCR1
LAZUCIRNON	2	CCR3
MOLIBRESIB	2	PARK7
RIVICICLIB	2	CDK6
ULECACICLIB	2	CDK6

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
CDK6	715	Binding:691, Functional:24
CCR1	243	Binding:176, Functional:67
CCR3	175	Binding:107, Functional:68
NOD2	126	Binding:121, Functional:5
ERAP1	88	Binding:85, Functional:2, ADMET:1
PARK7	62	Binding:62
TNFRSF1A	24	Binding:23, Functional:1
STAT4	20	Binding:20
IL23R	13	Binding:13
FUT2	2	Binding:2
NSMCE2	1	Binding:1
HLA-B	1	Binding:1
MEFV	1	Binding:1
MICA	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PARK7	3.5.1.124, 4.2.1.130	protein deglycase, D-lactate dehydratase
CDK6	2.7.11.22	cyclin-dependent kinase
ERAP1	3.4.11.1, 3.4.11.22	leucyl aminopeptidase, aminopeptidase I
ADA2	3.5.4.4	adenosine deaminase
ADO	1.13.11.19	cysteamine dioxygenase
FUT2	2.4.1.344, 2.4.1.69	type 2 galactoside alpha-(1,2)-fucosyltransferase, type 1 galactoside alpha-(1,2)-fucosyltransferase
MTMR3	3.1.3.95	phosphatidylinositol-3,5-bisphosphate 3-phosphatase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
CCR1	243
CCR3	175
CDK6	715
NOD2	126

Pharmacogenomics

Cohort genes with a PharmGKB record: 42; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
HLA-B	1

Chemical tractability of cohort targets

30 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
ABAMETAPIR	4	CCR1
RALTEGRAVIR	4	CCR1
PALBOCICLIB	4	CDK6
ABEMACICLIB	4	CDK6
RIBOCICLIB	4	CDK6
TRILACICLIB	4	CDK6
MOMELOTINIB	4	CDK6
SORAFENIB	4	CDK6
DABRAFENIB	4	CDK6
OLAPARIB	4	CDK6
PACLITAXEL	4	NOD2
DOCETAXEL ANHYDROUS	4	NOD2
GEFITINIB	4	NOD2
LEROCICLIB	3	CDK6
ALVOCIDIB	3	CDK6
DINACICLIB	3	CDK6
DALPICICLIB	3	CDK6
QUERCETIN	3	CDK6
DOVITINIB	3	CDK6
LESTAURTINIB	3	CDK6
METOCHALCONE	2	TNFRSF1A
AZD4818	2	CCR1
BX 471 FREE BASE	2	CCR1
BMS-817399	2	CCR1
CCX354	2	CCR1
BX 471	2	CCR1
LAZUCIRNON	2	CCR3
MOLIBRESIB	2	PARK7
RIVICICLIB	2	CDK6
ULECACICLIB	2	CDK6

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	CCR1, CDK6, NOD2
B	Phased (≥1) drug, not yet approved	4	TNFRSF1A, CCR3, PARK7, ERAP1
C	Druggable family + PDB, no drug	10	ADA2, IL23R, CNTN5, ADO, HLA-B, IFNGR1, IL12RB2, IL18R1, MICA, MICB
D	Druggable family + AlphaFold only, no drug	3	GUSBP1, FUT2, MTMR3
E	Difficult family or no structure, no drug	23	STAT4, TNFSF15, PSORS1C1, TFCP2L1, THADA, UBAC2, CPLX1, CCDC71, NSMCE2, LACC1 (+13 more)

Undrugged target profiles

36 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
LACC1	0	NOD2
STAT4	20	—
TNFSF15	0	—
GUSBP1	0	—
PSORS1C1	0	—
TFCP2L1	0	—
ADA2	0	—
IL23R	13	—
THADA	0	—
UBAC2	0	—
CNTN5	0	—
CPLX1	0	—
ADO	0	—
CCDC71	0	—
NSMCE2	1	—
HCG22	0	—
HORMAD2	0	—
DHFRP2	0	—
FUT2	2	—
IL12A-AS1	0	—
HLA-B	1	—
IRF8	0	—
IFNGR1	0	—
IL10	0	—
IL12A	0	—
IL12RB2	0	—
IL18R1	0	—
IRF5	0	—
JRKL	0	—
KLRC4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 82.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	52
PHASE2	15
PHASE3	10
PHASE1	3
PHASE4	1
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05879419	PHASE4	ACTIVE_NOT_RECRUITING	Recombinant Herpes Zoster Vaccine in Patients With Autoimmune Rheumatic Diseases
NCT04528082	PHASE3	RECRUITING	Apremilast Pediatric Study in Children With Active Oral Ulcers Associated With Behçet’s Disease
NCT05767047	PHASE3	RECRUITING	A Study of Apremilast in Children With Oral Ulcers Associated With Behçet’s Disease or Juvenile Psoriatic Arthritis
NCT06145893	PHASE3	RECRUITING	A Study of Efficacy and Safety of Hemay005 Tablets in Patients With Behçet’s Disease
NCT06780462	PHASE3	RECRUITING	Randomized Controlled Multicenter Study Comparing Steroid Therapy Plus Anticoagulants to Steroid Therapy Alone in Deep Venous Thrombosis of Behçet’s Syndrome
NCT06925698	PHASE3	NOT_YET_RECRUITING	Immunosuppressive Therapy Alone Versus Plus Oral Anticoagulation in the Treatment of VT Associated With Behcet’s Disease
NCT00995709	PHASE3	COMPLETED	Phase III Study in Refractory Behcet’s Disease
NCT01532570	PHASE3	COMPLETED	Clinical Study of TA-650 in Patients With Behcet’s Disease (BD) With Special Lesions
NCT02307513	PHASE3	COMPLETED	A Phase 3 Randomized, Double-blind Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Active Behçet’s Disease
NCT02505568	PHASE3	COMPLETED	A Study to Evaluate Efficacy and Safety of Infliximab in Participant With Moderate-to-Severe Refractory Intestinal Behcet’s Disease
NCT03209219	PHASE3	COMPLETED	Interferon α2a Versus Cyclosporine for Refractory Behçet’s Disease Uveitis
NCT06794008	PHASE2	RECRUITING	BCMA-CD19 CAR-T Therapy for Refractory Autoimmune Diseases
NCT00001865	PHASE2	COMPLETED	HAT in Eye Complications of Behcet’s Disease
NCT00483184	PHASE2	COMPLETED	Low Dose Interferon Alpha Treatment for Oral Ulcers of Behcet’s Disease
NCT00664599	PHASE2	COMPLETED	Rituximab for the Treatment of Severe Ocular Manifestations of Behcet’s Disease
NCT00700297	PHASE2	COMPLETED	Colchicine Randomized Double-Blind Controlled Crossover Study in Behcet’s Disease
NCT00866359	PHASE2	COMPLETED	A Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004) in the Treatment of Behçet Disease
NCT01693653	PHASE2	TERMINATED	Tocilizumab for the Treatment of Behcet’s Syndrome
NCT02620618	PHASE1/PHASE2	COMPLETED	Intravitreal Infliximab in Refractory Uveitis in Behcet’s Disease: A Safety and Efficacy Clinical Study
NCT02648581	PHASE2	COMPLETED	Efficacy and Safety of Ustekinumab, a Human Monoclonal Anti-IL-12/IL-23 Antibody, in Patients With Behçet Disease
NCT02756650	PHASE2	COMPLETED	1 Year of Treatment With Canakinumab in Behçet’s Disease Patients With Neurologic or Vascular Involvement
NCT03554161	PHASE2	TERMINATED	Tocilizumab for the Treatment of Refractory Behcet’s Uveitis
NCT04186559	PHASE2	UNKNOWN	Topical Pentoxifylline Gel on Behcet’s Disease Genital Ulcers
NCT04218565	PHASE2	TERMINATED	Golimumab for the Treatment of Refractory Behcet’s Uveitis
NCT04609397	PHASE2	TERMINATED	A Study to Evaluate the Efficacy and Safety of Hemay005 in the Treatment of Behçet Disease
NCT06386744	PHASE2	COMPLETED	Dusquetide for the Treatment of Behcet’s Disease
NCT07080346	PHASE2	COMPLETED	Upadacitinib for Refractory Behcet’s Syndrome
NCT06371417	PHASE1	RECRUITING	Phase 1b Trial of RAY121 in Immunological Diseases (RAINBOW Trial)
NCT06723106	PHASE1	ENROLLING_BY_INVITATION	Phase 1b Long-term Extension Trial of RAY121 in Immunological Diseases (RAINBOW-LTE Trial)
NCT00550498	PHASE1	TERMINATED	Stem Cell Transplantation in Ocular Lesions of Behcet’s Disease
NCT04334031	Not specified	RECRUITING	Deployment o the Multidisciplinary Prospective Cohort Imminent
NCT04402086	Not specified	RECRUITING	Rheumatology Patient Registry and Biorepository
NCT05200715	Not specified	RECRUITING	AutoInflammatory Disease Alliance Registry (AIDA)
NCT05904301	Not specified	RECRUITING	Armenian NAtionwide REGistry of Systemic Autoimmune and Autoinflammatory Diseases
NCT06451575	Not specified	RECRUITING	Thrombophilia and Thrombosis in Behçet’s Disease
NCT06729112	Not specified	RECRUITING	Pan-immune-inflammation Value (PIN) in Behçet’s Disease and Its Correlation With Disease Activity
NCT06730958	Not specified	RECRUITING	Evaluation of Serum Follistatin-Like Protein 1 Levels in Behcet’s Disease and Its Association With Disease Activity
NCT06836817	Not specified	NOT_YET_RECRUITING	Evaluation of Voice in Behcet’s
NCT07039903	Not specified	NOT_YET_RECRUITING	A Novel Psychological Intervention for Adults With Bipolar Disorder and Attention Deficit Hyperactivity Disorder Comorbidity (VECTOR)
NCT07065747	Not specified	RECRUITING	Quantification & Classification of Inflammatory Cells in Uveitis Using OCT

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
APREMILAST	4	4
CANAKINUMAB	4	1
DACLIZUMAB	4	1
GOLIMUMAB	4	1
INTERFERON ALFA-2A	4	1
SECUKINUMAB	4	1
UPADACITINIB	4	1
USTEKINUMAB	4	1
MUFEMILAST	3	2
DUSQUETIDE	3	1
ZINC GLUCONATE	3	1
BUTYRIC ACID	2	1
CHEMBL475165	0	3
CHEMBL4783966	0	1